Catheter balloon methods and apparatus employing sensing elements

ABSTRACT

An apparatus for medical diagnosis and/or treatment is provides. The apparatus includes a flexible substrate forming an inflatable body and a plurality of sensing elements disposed on the flexible substrate. The plurality of sensing elements are disposed about the inflatable body such that the sensing elements are disposed at areas of minimal curvature of the inflatable body in a deflated state.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims priority to U.S. provisional application Ser.No. 61/515,713, filed Aug. 5, 2011, entitled “Catheter Balloon Methodsand Apparatus Employing Lumen Contact Sensors,” which is herebyincorporated herein by reference in its entireties.

BACKGROUND

High quality medical sensing and imaging data has become increasinglybeneficial in the diagnoses and treatment of a variety of medicalconditions. The conditions can be associated with the digestive system,the cardio-circulatory system, and can include injuries to the nervoussystem, cancer, and the like.

For example, complex fractionated electrogram (CFAE) triggers within theright and left atria play a role in the pathogenesis of persistent andpermanent atrial fibrillation, atrial flutters, and tachycardias. Radiofrequency (RF) energy (delivered via point bipolar electrodes) can beused to ablate tissues to correct aberrant conduction pathways, aided byimaging data.

SUMMARY

The Inventors have recognized and appreciated that inflatable bodiesthat include sensing elements can provide data measurements that couldbeneficial medical diagnosis and/or treatment. The inventors have alsorecognized that such systems can be made more robust to the use inmedical diagnosis and/or treatment environment, provide usefulmeasurements of tissue states (including amount of contact with thetissue), and maintain optimal performance, if the sensing elements areselectively disposed at certain regions of the inflatable body. In viewof the foregoing, various embodiments herein are directed generally tomethods, apparatus and systems for medical diagnosis and/or treatmentthat include a flexible substrate forming an inflatable body and aplurality of sensing elements disposed on the flexible substrate, wherethe sensing elements are selectively disposed at certain regions of theinflatable body.

In some examples herein, an apparatus is provided for medical diagnosisand/or treatment that includes a flexible substrate forming aninflatable body and a plurality of sensing elements disposed on theflexible substrate. The plurality of sensing elements is disposed aboutthe inflatable body such that the sensing elements are disposed at areasof minimal curvature of the inflatable body in a deflated state.

The present disclosure provides some examples of an apparatus formedical diagnosis and/or treatment that include a flexible substrateforming an inflatable body, a coupling bus disposed about a region ofthe inflatable body, and a plurality of sensing elements disposed on theflexible substrate. The plurality of sensing elements are coupled to thecoupling bus and the plurality of sensing elements are disposed about aportion of a circumference of the inflatable body such that the sensorelements are disposed at areas of minimal curvature of the inflatablebody in a deflated state.

The coupling bus may be a serpentine bus and the serpentine bus mayelectrically couple the plurality of sensing elements.

In some examples, the apparatus includes an encapsulation materialdisposed over substantially a portion of the coupling bus. Theencapsulation material may include a polyurethane.

In some examples, the apparatus includes a shaft coupled to theinflatable body, a flex board disposed over or inside the shaft, aplurality of wires connected to the flex board to provide and/or obtainelectrical signals to the flex board, and an intermediate buselectrically coupled to a flex board and to the plurality sensors. Theplurality of sensing elements may include at least one of a pressuresensor or an impedance sensor.

The shaft may include a cryoablation device, a laser ablation device, ahigh intensity ultrasound or a RF device, in some examples.

In some examples, the sensing elements of the apparatus are disposed ina longitudinal direction along portions of the inflatable body thatexperience minimal strain when the inflatable body is in a deflatedstate.

In some examples, the coupling bus is an annular bus, and the annularbus is disposed as a ring substantially about a circumference of theinflatable body.

The coupling bus of the apparatus is a serpentine bus including aplurality of serpentine structures, in accordance with some examples.

One or more of the sensing elements of the plurality of sensing elementsmay include contact sensors, in some examples.

In some examples, the plurality of sensing elements is disposed about anequator of the inflatable body.

In some examples, the plurality of sensing elements is disposedproximate to a distal portion of the inflatable body.

In some examples, the plurality of sensing elements of the apparatus isdisposed in helical pattern about the inflatable body.

In some examples, the apparatus includes an encapsulation layer disposedover the plurality of sensing elements. The encapsulation layer mayposition the sensing elements at a neutral mechanical plane.

The encapsulation layer may include a polymer, in some examples.

In some examples, the apparatus includes at least one intermediate layerdisposed between the plurality of sensing elements and the inflatablebody, where the at least one intermediate layer positions the sensingelements at the neutral mechanical plane.

In some examples, the inflatable body is disposed near a distal end of acatheter.

In some examples, the inflatable body is a balloon. The balloon may becylindrical, onion-shaped, cone-shaped, dog-bone-shaped, andbarrel-shaped.

The coupling bus may have a T-configuration or an annular ringstructure.

In some examples, the apparatus includes an encapsulation materialdisposed over substantially a portion of the plurality of sensingelements. The encapsulation material may include polyurethane.

In some examples, the sensing elements are formed from a conductivematerial.

In some examples, the coupling bus is formed from a conductive material.

The present disclosure provides some examples of a method of fabricatingan apparatus for medical diagnosis and/or treatment. The example methodincludes providing a coupling bus that is coupled to a plurality ofsensing elements, disposing the coupling bus about a region of aninflatable body, and disposing the plurality of sensing elements about aportion of a circumference of the inflatable body such that the sensorelements are disposed at areas of minimal curvature of the inflatablebody.

The method may include extracting the coupling bus and the plurality ofsensing elements from a carrier substrate prior to disposing thecoupling bus about the region of the inflatable body.

In some examples, the disposing the coupling bus about the region of theinflatable body includes applying the coupling bus using a dissolvabletape backing.

In some examples, the coupling bus is disposed near a distal region ofthe inflatable body and the plurality of sensing elements is disposedcloser to a mid-portion of the inflatable body.

The present disclosure provides some examples of a method of performinga medical diagnosis and/or treatment on a tissue that include disposingin proximity to the tissue an apparatus including a flexible substrateforming an inflatable body, a coupling bus, and a plurality of sensingelements that are coupled to the coupling bus. The one or more sensingelements of the plurality of sensing elements include contact sensors.The coupling bus is disposed near a distal end of the inflatablesubstrate. The plurality of sensing elements is disposed about theinflatable body such that the sensing elements are disposed at areas ofminimal curvature of the inflatable body. The method further includesrecording a measurement of at least one sensing element of the pluralityof sensing elements. The measurement provides an indication of a stateof a portion of the tissue.

In some examples, the measurement provides an indication of a diseasestate of the portion of the tissue.

In some examples, the measurement provides an indication of a contactstate of the portion of the tissue with the at least one sensing elementof the plurality of sensing elements.

The present disclosure provides examples of an apparatus for displayinga representation of measurements of a plurality of sensing elementsdisposed about at least a portion of a circumference of an inflatablebody during a medical diagnosis and/or treatment of a tissue. Theapparatus includes display, a memory storing machine-readableinstructions, and one or more processor units to execute themachine-readable instructions. The execution of the machine-readableinstructions causes the display to display the representation of themeasurements. In this example, the representation includes (i) aplurality of first indicators, each first indicator corresponding to asensing element of the plurality of sensing elements that measures asignal below a threshold value, and (ii) a plurality of secondindicators, each second indicator corresponding to a sensing element ofthe plurality of sensing elements that measures a signal above thethreshold value.

In some examples, the measurement below the threshold value indicatesthat the corresponding sensing element of the plurality of sensingelements is not in contact with the tissue.

In some examples, the measurement above the threshold value indicatesthat at least a portion of the corresponding sensing element of theplurality of sensing elements is in contact with the tissue.

The present disclosure provides examples of an apparatus for displayinga representation of measurements of a plurality of sensing elementsdisposed about at least a portion of a circumference of an inflatablebody during a medical diagnosis and/or treatment of a tissue. Theapparatus includes a display, a memory storing machine-readableinstructions, and one or more processor units to execute themachine-readable instructions. In this example, the execution of themachine-readable instructions causes the display to display therepresentation of the measurements. In this example, the representationincludes (i) a plurality of first spatial representations, each firstspatial representation corresponding to a sensing element of theplurality of sensing elements that is disposed at a first latitude ofthe inflatable body, and (ii) a plurality of second spatialrepresentations, each second spatial representation corresponding to asensing element of the plurality of sensing elements that is disposed ata second latitude of the inflatable body that is different from thefirst latitude.

In some examples, each of the first spatial representations or each ofthe second spatial representations displays a first indication if thecorresponding sensing element measures a signal above a threshold value.

In some examples, each of the first spatial representations or each ofthe second spatial representations displays a second indication if thecorresponding sensing element measures a signal below a threshold value.

The present disclosure provides examples of a stretchable electronicsystem. The stretchable electronic system includes a flexible annularinterconnect and a first plurality of electrodes coupled to the flexibleannular interconnect.

In some examples, the flexible annular interconnect has a first radiusand each electrode in the first plurality of electrodes is coupled tothe flexible annular interconnect via at least one flexible connectorextending from the annular interconnect such that the first plurality ofelectrodes are positioned at a second radius distinct from the firstradius.

In some examples, the flexible annular interconnect is formed from aconductive material.

In some examples, the second radius is greater than the first radius.

The stretchable electronic may include a second plurality of electrodescoupled to the flexible annular interconnect. Each electrode in thesecond plurality of electrodes may be coupled to the flexible annularinterconnect via the at least one flexible connector extending from theannular interconnect such that the second plurality of electrodes arepositioned at a third radius, distinct from the first and second radii.

In some examples, the third radius is greater than the second radius.

In some examples, the stretchable electronic system includes a flexiblesubstrate forming an inflatable body. The flexible annular interconnectand the first plurality of electrodes may be coupled to a peripheralportion of the flexible substrate.

In some examples, the inflatable body is disposed near a distal end of acatheter.

The inflatable body may be a balloon. The balloon may be cylindrical,onion-shaped, cone-shaped, dog-bone-shaped, and barrel-shaped.

In some examples, the flexible annular interconnect comprises at leastone intermediate bus for electronically connecting each electrode withan electrical source.

In some examples, the flexible annular interconnect has a serpentinemorphology.

The stretchable electronic system may also include a flexible substrateforming an inflatable body coupled to the flexible annular interconnect.The flexible annular interconnect may have a T-configuration or anannular ring structure. The flexible annular interconnect may have aT-configuration or an annular ring structure.

In some examples, the stretchable electronic system includes anencapsulation material disposed over at least a portion of the flexibleannular interconnect or the plurality of sensing elements. Theencapsulation material may include polyurethane.

In some examples, the stretchable electronic system includes anintermediate layer disposed between the flexible annular interconnect.

The present disclosure provides examples of a system for mapping contactwith a surface. The system includes an inflatable body, a plurality ofelectrodes coupled to the inflatable body, and an electronic displayelectrically coupled to the plurality of electrodes, the electronicdisplay providing a visual representation of the spatial location of theplurality of electrodes on the inflatable body. The electronic displaychanges a visual attribute of an electrode in the plurality ofelectrodes in response to a change in an electrical signal produced bythe electrode. The change in the electrical signal identifies a contactcondition of the electrode with respect to the surface.

In different examples, the visual attribute is a binary representationor a quantitative representation.

The present disclosure provides examples of a stretchable electronicsystem that include a flexible interconnect and a plurality of impedancebased electrode pairs coupled to the flexible interconnect. Theelectrode pairs measure impedance between two electrodes of theelectrode pair.

The present disclosure provides some examples of a method ofmanufacturing a contact mapping balloon catheter. The method includesidentifying regions of maximum curvature on the balloon of the ballooncatheter when the balloon is in a deflated state and coupling aplurality of electrodes to the balloon such that the plurality ofelectrodes are positioned outside of the regions of maximum curvature.

In accordance with examples disclosed herein, co-locating contactsensors (electrical, pressure, thermal or otherwise) with thetherapeutic facility (which may comprise any circuitry and elements todelivery ablation described herein) can reduce or eliminate the need fordyes and may reduce the time to complete the procedure. Further, examplesystems and apparatus disclosed herein can be implemented to bothdeliver the ablative therapy and the same device during the sameprocedure can be implemented to generate data regarding of theelectrical conductivity of the site post-ablation.

The following publications, patents, and patent applications are herebyincorporated herein by reference in their entirety:

Kim et al., “Stretchable and Foldable Silicon Integrated Circuits,”Science Express, Mar. 27, 2008, 10.1126/science.1154367;

Ko et al., “A Hemispherical Electronic Eye Camera Based on CompressibleSilicon Optoelectronics,” Nature, Aug. 7, 2008, vol. 454, pp. 748-753;

Kim et al., “Complementary Metal Oxide Silicon Integrated CircuitsIncorporating Monolithically Integrated Stretchable Wavy Interconnects,”Applied Physics Letters, Jul. 31, 2008, vol. 93, 044102;

Kim et al., “Materials and Noncoplanar Mesh Designs for IntegratedCircuits with Linear Elastic Responses to Extreme MechanicalDeformations,” PNAS, Dec. 2, 2008, vol. 105, no. 48, pp. 18675-18680;

Meitl et al., “Transfer Printing by Kinetic Control of Adhesion to anElastomeric Stamp,” Nature Materials, January, 2006, vol. 5, pp. 33-38;

U.S. Patent Application publication no. 2010 0002402-A1, published Jan.7, 2010, filed Mar. 5, 2009, and entitled “STRETCHABLE AND FOLDABLEELECTRONIC DEVICES;”

U.S. Patent Application publication no. 2010 0087782-A1, published Apr.8, 2010, filed Oct. 7, 2009, and entitled “CATHETER BALLOON HAVINGSTRETCHABLE INTEGRATED CIRCUITRY AND SENSOR ARRAY;”

U.S. Patent Application publication no. 2010 0116526-A1, published May13, 2010, filed Nov. 12, 2009, and entitled “EXTREMELY STRETCHABLEELECTRONICS;”

U.S. Patent Application publication no. 2010 0178722-A1, published Jul.15, 2010, filed Jan. 12, 2010, and entitled “METHODS AND APPLICATIONS OFNON-PLANAR IMAGING ARRAYS;” and

U.S. Patent Application publication no. 2010 027119-A1, published Oct.28, 2010, filed Nov. 24, 2009, and entitled “SYSTEMS, DEVICES, ANDMETHODS UTILIZING STRETCHABLE ELECTRONICS TO MEASURE TIRE OR ROADSURFACE CONDITIONS.”

Kim, D. H. et al. (2010). Dissolvable films of silk fibroin forultrathin conformal bio-integrated electronics. Nature Materials, 9,511-517.

Omenetto, F. G. and D. L. Kaplan. (2008). A new route for silk. NaturePhotonics, 2, 641-643.

Omenetto, F. G., Kaplan, D. L. (2010). New opportunities for an ancientmaterial. Science, 329, 528-531.

Halsed, W. S. (1913). Ligature and suture material. Journal of theAmerican Medical Association, 60, 1119-1126.

Masuhiro, T., Yoko, G., Masaobu, N., et al. (1994). Structural changesof silk fibroin membranes induced by immersion in methanol aqueoussolutions. Journal of Polymer Science, 5, 961-968.

Lawrence, B. D., Cronin-Golomb, M., Georgakoudi, I., et al. (2008).Bioactive silk protein biomaterial systems for optical devices.Biomacromolecules, 9, 1214-1220.

Demura, M., Asakura, T. (1989). Immobilization of glucose oxidase withBombyx mori silk fibroin by only stretching treatment and itsapplication to glucose sensor. Biotechnololgy and Bioengineering, 33,598-603.

Wang, X., Zhang, X., Castellot, J. et al. (2008). Controlled releasefrom multilayer silk biomaterial coatings to modulate vascular cellresponses. Biomaterials, 29, 894-903.

U.S. patent application Ser. No. 12/723,475 entitled “SYSTEMS, METHODS,AND DEVICES FOR SENSING AND TREATMENT HAVING STRETCHABLE INTEGRATEDCIRCUITRY,” filed Mar. 12, 2010.

U.S. patent application Ser. No. 12/686,076 entitled “Methods andApplications of Non-Planar Imaging Arrays,” filed Jan. 12, 2010.

U.S. patent application Ser. No. 12/636,071 entitled “Systems, Methods,and Devices Using Stretchable or Flexible Electronics for MedicalApplications,” filed Dec. 11, 2009.

U.S. patent application Ser. No. 12/616,922 entitled “ExtremelyStretchable Electronics,” filed Nov. 12, 2009.

U.S. patent application Ser. No. 12/575,008 entitled “Catheter BalloonHaving Stretchable Integrated Circuitry and Sensor Array,” filed on Oct.7, 2009.

U.S. patent application Ser. No. 13/336,518 entitled “Systems, Methods,and Devices Having Stretchable Integrated Circuitry for Sensing andDelivering Therapy,” filed Dec. 23, 2011.

Further combinations and sub-combinations of various concepts areprovided below in the claims section. It should be appreciated that allcombinations of such concepts and additional concepts described ingreater detail below (provided such concepts are not mutuallyinconsistent) are contemplated as being part of the inventive subjectmatter disclosed herein. In particular, all combinations of subjectmatter appearing as numbered claims at the end of this disclosure arecontemplated as being part of the inventive subject matter disclosedherein. In addition, all combinations of subject matter supported bythis disclosure, including the drawings, the description and the claims,are contemplated as being part of the inventive subject matter even ifnot expressly recited as one of the numbered claims.

It should be appreciated that all combinations of the foregoing conceptsand additional concepts described in greater detail below (provided suchconcepts are not mutually inconsistent) are contemplated as being partof the inventive subject matter disclosed herein. In particular, allcombinations of claimed subject matter appearing at the end of thisdisclosure are contemplated as being part of the inventive subjectmatter disclosed herein. It should also be appreciated that terminologyexplicitly employed herein that also may appear in any disclosureincorporated by reference should be accorded a meaning most consistentwith the particular concepts disclosed herein.

BRIEF DESCRIPTION OF THE DRAWINGS

The skilled artisan will understand that the drawings primarily are forillustrative purposes and are not intended to limit the scope of theinventive subject matter described herein. The drawings are notnecessarily to scale; in some instances, various aspects of theinventive subject matter disclosed herein may be shown exaggerated orenlarged in the drawings to facilitate an understanding of differentfeatures. In the drawings, like reference characters generally refer tolike features (e.g., functionally similar and/or structurally similarelements).

FIG. 1 illustrates an example illustration of an incomplete occlusion ofthe ostium or pulmonary vein by a catheter balloon, where a dye isdeployed to help visualization of the incomplete occlusion according tothe principles described herein.

FIG. 2A shows an example scanning electron microscope image with astretchable design, according to the principles described herein.

FIG. 2B shows an example scanning electron microscope image with anotherstretchable design, according to the principles described herein.

FIG. 2C shows an example scanning electron microscope image with anotherstretchable design, according to the principles described herein.

FIG. 3A illustrates a view of an example of a stretchable electronicsystem, according to the principles described herein.

FIG. 3B illustrates another view of the example of the stretchableelectronic system of FIG. 3A, according to the principles describedherein.

FIG. 4A shows a view of portions of the example stretchable electronicsystem of FIGS. 3A and 3B, according to the principles described herein.

FIG. 4B shows another view of portions of the example stretchableelectronic system of FIGS. 3A and 3B, according to the principlesdescribed herein.

FIG. 4C shows another view of portions of the example stretchableelectronic system of FIGS. 3A and 3B, according to the principlesdescribed herein.

FIG. 5A illustrates an example of a stretchable electronic system,according to the principles described herein.

FIG. 5B illustrates another view of the example of the stretchableelectronic system of FIG. 5A, according to the principles describedherein.

FIG. 5C illustrates another view of the example of the stretchableelectronic system of FIG. 5A, according to the principles describedherein.

FIG. 5D illustrates another view of the example of the stretchableelectronic system of FIG. 5A, according to the principles describedherein.

FIG. 6 illustrates an example pair of sensors with polyimide on thebackplane and serpentine interconnects branching from the sensors,according to the principles described herein.

FIG. 7 shows the stretchable electronic system according to theprinciples of FIGS. 3A and 3B, disposed on an example inflatable body,according to the principles described herein.

FIG. 8 is a magnified view of the example balloon catheter of FIG. 7,according to the principles described herein.

FIG. 9A illustrates an example of a stretchable electronic system,according to the principles described herein.

FIG. 9B illustrates another view of the example of the stretchableelectronic system of FIG. 9A, according to the principles describedherein.

FIG. 9C illustrates another view of the example of the stretchableelectronic system of FIG. 9A, according to the principles describedherein.

FIG. 9D illustrates another view of the example of the stretchableelectronic system of FIG. 9A, according to the principles describedherein.

FIG. 10A illustrates another example of a stretchable electronic system,according to the principles described herein.

FIG. 10B illustrates another view of the example of the stretchableelectronic system of FIG. 10A, according to the principles describedherein.

FIG. 10C illustrates another view of the example of the stretchableelectronic system of FIG. 10A, according to the principles describedherein.

FIG. 10D illustrates another view of the example of the stretchableelectronic system of FIG. 10A, according to the principles describedherein.

FIG. 11A illustrates an example of a stretchable electronic system,according to the principles described herein.

FIG. 11B illustrates an exploded view of the example of the stretchableelectronic system of FIG. 11A as indicated by the circular callout line11B in FIG. 11A, according to the principles described herein.

FIG. 11C illustrates another view of the example of the stretchableelectronic system of FIG. 11A as indicated by the circular callout line11C in FIG. 11B, according to the principles described herein.

FIG. 11D illustrates another view of the example of the stretchableelectronic system of FIG. 11A as indicated by the circular callout line11D in FIG. 11C, according to the principles described herein.

FIG. 12A illustrates a step in the assembly of an example stretchableelectronic system, according to the principles described herein.

FIG. 12B illustrates another step in the assembly of an examplestretchable electronic system, according to the principles describedherein.

FIG. 12C illustrates another step in the assembly of an examplestretchable electronic system, according to the principles describedherein.

FIG. 13A illustrates a magnified view of example integrated componentsof the electrode design of FIG. 13C, as indicated by the circularcallout line 13A in FIG. 13C, according to the principles describedherein.

FIG. 13B illustrates another magnified view of example integratedcomponents of the electrode design of FIG. 13C, as indicated by thecircular callout line 13B in FIG. 13C, according to the principlesdescribed herein.

FIG. 13C illustrates an electrode design, according to the principlesdescribed herein.

FIG. 14A shows an example application of a metallization layer of astretchable electronic system, according to the principles describedherein.

FIG. 14B shows another view of the example application of themetallization layer of a stretchable electronic system, according to theprinciples described herein.

FIG. 15A shows an example application of a polyimide layer of astretchable electronic system, according to the principles describedherein.

FIG. 15B shows another view of the example application of the polyimidelayer of a stretchable electronic system, according to the principlesdescribed herein.

FIG. 16 provides an example of a plurality of stretchable electronicsystems positioned on a wafer, according to the principles describedherein.

FIG. 17A is an example diagram illustrating a ballooninflation/deflation process, according to the principles describedherein.

FIG. 17B is an example diagram further illustrating a ballooninflation/deflation process, according to the principles describedherein.

FIG. 18A illustrates an example of a catheter balloon in an inflatedstate, according to the principles described herein.

FIG. 18B illustrates an example of the catheter balloon of FIG. 18A in adeflated state, according to the principles described herein.

FIG. 18C illustrates another view of the catheter balloon of FIGS. 18Aand 18B in describing a transition between an inflated and a deflatedstate, according to the principles described herein.

FIG. 19 is a schematic of a folded section of an example deflatedballoon, according to the principles described herein.

FIG. 20 is a graph illustrating example computation of the change instrain along a folded section of a deflated balloon, according to theprinciples described herein.

FIG. 21 is a schematic illustrating an example balloon catheterintegrated with a flexible electrode configuration, according to theprinciples described herein.

FIG. 22 are a flow chart illustrating a non-limiting example process forfabricating an stretchable electronic system and integrating thestretchable electronic system with a balloon catheter, according to theprinciples described herein.

FIG. 23A is an example of the layers of a balloon and an integratedelectrode configuration implemented to position the electricalcomponents in a neutral mechanical plane, according to the principlesdescribed herein.

FIG. 23B is an example of the layers of a balloon and an integratedelectrode configuration implemented to position the electricalcomponents in a neutral mechanical plane, according to the principlesdescribed herein.

FIG. 24 illustrates an example flex ribbon connector for electricallycoupling a plurality of electrodes on an inflatable body with a remotesource, according to the principles described herein.

FIG. 25 illustrates an example T-shaped sensing element configuration,according to the principles described herein.

FIG. 26 illustrates an example T-shaped sensing element configuration nincluding an interface between a coupling bus and a flexible printedcircuit board (PCB) positioned on a catheter shaft, according to theprinciples described herein.

FIG. 27 illustrates an example T-shaped sensing element disposed over aninflatable body, according to one example, according to the principlesdescribed herein.

FIG. 28 a schematic diagram of an example flex boar, according to theprinciples described herein.

FIG. 29A illustrates an example schematic plan for a flex board design,according to the principles described herein.

FIG. 29B illustrates another example schematic plan for a flex boarddesign, according to the principles described herein.

FIG. 30 illustrates the bottom layer of the example flex board,according to the principles described herein.

FIG. 31 illustrates a top layer of the example flex board, according tothe principles described herein.

FIG. 32 illustrates an encapsulation layer of the example flex board,according to the principles described herein.

FIG. 33 illustrates a stage in an example fabrication process of aballoon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 34 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 35 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 36 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 37 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 38 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 39 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 40 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 41 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 42 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 43 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 44 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 45 illustrates another stage in the example fabrication process ofa balloon catheter with an array of sensing elements in a stretchableelectronic system, according to the principles described herein.

FIG. 46 shows a schematic example of a balloon catheter includingintegrating electrodes coupled with a data acquisition and graphicaluser interface, according to the principles described herein.

FIG. 47 shows an example circuit diagram of a unidirectional constantcurrent source used for impedance measurements data, according to theprinciples described herein.

FIG. 48 shows an example circuit diagram of a bidirectional, lowdistortion current source used for impedance measurements data,according to the principles described herein.

FIG. 49 provides a series of screen shots of an example graphical userinterface demonstrating a variety of conditions simulated with a ballooncatheter including integrated sensing electronics positioned in a glassheart, according to the principles described herein.

FIG. 50 provides a series of screen shots of an example graphical userinterface demonstrating a variety of contact conditions with a ballooncatheter including integrated sensing electronics positioned in a tissuelumen of a live pig, according to the principles described herein.

FIG. 51A illustrates an example visualization of contact sensing frommeasured data, according to the principles described herein.

FIG. 51B illustrates another example visualization of contact sensingfrom measured data, according to the principles described herein.

FIG. 52 demonstrates another example user interface displaying binaryread outs of sensors disposed on a balloon catheter, according to theprinciples described herein.

FIG. 53 demonstrates an example user interface displaying quantitativeread outs of sensors disposed on a balloon catheter, according to theprinciples described herein.

FIG. 54 demonstrates another example user interface displayingquantitative read outs of sensors disposed on a balloon catheter,according to the principles described herein.

FIG. 55A illustrates an example determination of whether contact is madeto blood based on changes in electrical conductivity or resistivity,according to the principles described herein.

FIG. 55B illustrates an example determination of whether contact is madeto tissue based on changes in electrical conductivity or resistivity,according to the principles described herein.

FIG. 56 shows example pressure sensitive resistor (PSR) contact sensorin inferior vena cava/superior vena cava (IVC/SVC) data, according tothe principles described herein.

FIG. 57 illustrates example electrical impedance tomography (EIT)contact sensors in IVC data, according to the principles describedherein.

FIG. 58 illustrates example filtered EIT data, according to theprinciples described herein.

FIG. 59A illustrates an example of a sensor configuration on a balloonsurface, according to the principles described herein.

FIG. 59B illustrates an additional example of a sensor configuration ona balloon surface, according to the principles described herein.

FIG. 59C illustrates an additional example of a sensor configuration ona balloon surface, according to the principles described herein.

FIG. 60A illustrates a further example of a sensor array, according tothe principles described herein.

FIG. 60B illustrates an additional example of a sensor array, includingan “L” shaped array, according to the principles described herein.

FIG. 61A illustrates an example of a multi-electrode and ballooncatheter device, according to the principles described herein.

FIG. 61B illustrates another example of a multi-electrode and ballooncatheter device, according to the principles described herein.

FIG. 61C illustrates another example of a multi-electrode and ballooncatheter device, according to the principles described herein.

FIG. 61D illustrates another example of a multi-electrode and ballooncatheter device, according to the principles described herein.

FIG. 61E illustrates another example of a multi-electrode and ballooncatheter device, according to the principles described herein.

FIG. 61F illustrates another example of a multi-electrode and ballooncatheter device, according to the principles described herein.

FIG. 61G illustrates another example of a multi-electrode and ballooncatheter device, according to the principles described herein.

FIG. 62 illustrates example dense arrays of conformal electrodes withmetal serpentine interconnects on thin polymeric sheets, according tothe principles described herein.

FIG. 63A illustrates an example of an endocardial application of theapparatus and methods, according to the principles described herein.

FIG. 63B illustrates another example of an endocardial application ofthe apparatus and methods, according to the principles described herein.

FIG. 63C illustrates another example of an endocardial application ofthe apparatus and methods, according to the principles described herein.

FIG. 64A shows an example of an apparatus including strainsensors/gauges, according to the principles described herein.

FIG. 64B shows another example of an apparatus including strainsensors/gauges, according to the principles described herein.

FIG. 64C shows another example of an apparatus including strainsensors/gauges, according to the principles described herein.

FIG. 65A illustrates an example sensing modalities including temperaturesensor arrays co-located with sensing elements, according to theprinciples described herein.

FIG. 65B illustrates additional example sensing modalities, includingtemperature sensor and electrode arrays, according to the principlesdescribed herein.

FIG. 65C illustrates an example of applying the methods and apparatuswith respect to a cryo lesion and RF lesion, according to the principlesdescribed herein.

The features and advantages of the various examples will become moreapparent from the detailed description set forth below when taken inconjunction with the drawings.

DETAILED DESCRIPTION

Following below are more detailed descriptions of various conceptsrelated to, and examples of inventive systems, methods and apparatus foruse with balloon catheters and other types of catheters. The systems,methods and apparatus used for medical diagnosis and/or treatment. Itshould be appreciated that various concepts introduced above anddescribed in greater detail below may be implemented in any of numerousways, as the disclosed concepts are not limited to any particular mannerof implementation. Examples of specific implementations and applicationsare provided primarily for illustrative purposes.

As used herein, the term “includes” means includes but not limited to,the term “including” means including but not limited to. The term “basedon” means based at least in part on.

An example system, method and apparatus described herein can be used formedical diagnosis and/or treatment. The example apparatus can include aflexible substrate that forms an inflatable body and a plurality ofsensing elements disposed on the flexible substrate. The plurality ofsensing elements can be disposed about the inflatable body such that thesensing elements are disposed at areas of minimal curvature of theinflatable body in a deflated state (which includes a collapsed state).

In any example described herein, an area of minimal curvature maycorrespond to, and/or lie proximate to, regions of low and/or minimalstrain in the inflatable body in the deflated state.

In an example, the inflatable body can be formed from any suitableflexible and/or stretchable material in the art. Non-limiting examplesinclude polyethylene terephthalate (PET), polyurethane, and nylon.

In an example, the inflatable body can be configured as an expandableportion positioned near an end of a catheter. In non-limiting examples,the inflatable body can be a balloon catheter. For example, theinflatable body can be a balloon having a cylindrical morphology, a coneshaped morphology or dog-bone shaped morphology, an “onion”-shapedmorphology (i.e., a shape that can exhibit different curvatures in x-and y-directions), or a barrel-like morphology. In another example, theinflatable body may have a compound shape. For example, the inflatablebody may be rounded in shape in certain portions, and include at leastone portion that is flattened. In another example, the inflatable bodymay be configured as a flattened stretchable portion that can beexpanded or collapsed. In an example implementation, such a flattenedportion of the inflatable body may be deployed to make substantiallyfull contact with a portion of a tissue, e.g., as part of a tissuelumen.

Non-limiting examples of a tissue lumen according to the principles ofany of the examples described herein include the channel within atubular tissue structure, such as but not limited to a blood vessel(including an artery or a vein), or to the cavity within a hollowportion of an organ, such as but not limited to an intestine, an oralcanal, a heart, a kidney, or auditory canal,

Another example system, method and apparatus described herein that canbe used for medical diagnosis and/or treatment includes a flexiblesubstrate that forms an inflatable body, a coupling bus disposed about aregion of the inflatable body, and a plurality of sensing elementsdisposed on the flexible substrate. The plurality of sensing elementsare coupled to the coupling bus. Also, the plurality of sensing elementsare disposed about a portion of a circumference of the inflatable bodysuch that the sensor elements are disposed at areas of minimal curvatureof the inflatable body in a deflated state (which includes a collapsedstate).

In an example, the coupling bus is disposed near a distal region of theinflatable body and the plurality of sensing elements are disposedcloser to a mid-portion of the inflatable body.

In another example, the coupling bus is disposed near a mid-portion ofthe inflatable body and the plurality of sensing elements are disposedcloser to a distal region of the inflatable body.

An example electronic structure according to the principles hereinincludes a coupling bus and a plurality of sensing elements that arecoupled to the coupling bus. In an example, the plurality of sensingelements can be configured to extend to substantially the same distanceor radius from the coupling bus. In another example, one or more sensingelement of the plurality of sensing elements can be configured to extenda different distance from the coupling bus than that of the othersensing elements of the plurality of sensing elements. For example, anumber of the plurality of sensors can extend to a first distance ofradius from the coupling bus, while the remaining sensors can all extendto a second distance or radius greater than the first. In yet anotherexample, the plurality of sensing elements can extend to three differentdistances or radii from the coupling bus.

In an example, the coupling bus can include conductive portions thatfacilitate electrical communication between the sensing elements and anexternal circuit. For applications where a high conductivity isbeneficial, a metal or metal alloy may be used, including but notlimited to aluminum or a transition metal (including copper, silver,gold, platinum, zinc, nickel, chromium, or palladium, or any combinationthereof) and any applicable metal alloy, including alloys with carbon.Suitable conductive materials may include a semiconductor-basedconductive material, including a silicon-based conductive material,indium tin oxide, or Group III-IV conductor (including GaAs).

In another example, the coupling bus can include such conductiveportions and also non-conductive portions. Such non-conductive portionscan be used to achieve a symmetric shape and/or weight distribution ofthe coupling bus, to introduce a mechanical stability to the couplingbus-sensing elements system, to reduce or eliminate a strain at ajunction between a connector from the sensing element and the couplingbus, to encapsulate the conductive portions for performance, electricaland or mechanical stability, and/or to isolate the conductive portionsfrom an external strain applied to the system during use in a medicaldiagnostic and /or treatment procedure. The non-conductive portion canbe a polymeric material, such as but not limited to a polyimide, apolyethylene terephthalate (PET), or a polyeurethane. Other non-limitingexamples of applicable polymeric materials include plastics, elastomers,thermoplastic elastomers, elastoplastics, thermostats, thermoplastics,acrylates, acetal polymers, biodegradable polymers, cellulosic polymers,fluoropolymers, nylons, polyacrylonitrile polymers, polyamide-imidepolymers, polyarylates, polybenzimidazole, polybutylene, polycarbonate,polyesters, polyetherimide, polyethylene, polyethylene copolymers andmodified polyethylenes, polyketones, poly(methyl methacrylate,polymethylpentene, polyphenylene oxides and polyphenylene sulfides,polyphthalamide, polypropylene, polyurethanes, styrenic resins, sulphonebased resins, vinyl-based resins, or any combinations of thesematerials. In an example, a polymer herein can be a DYMAX® polymer(Dymax Corporation, Torrington, Conn.). or other UV curable polymer.

In an example, the coupling bus can be shaped as an annular ringstructure, an oval structure, a polygonal structure, such as but notlimited to a pentagonal, hexagonal or octagonal structure, or otherclosed-loop structure. In another example, the coupling bus can be astructure with arms or other extending open-loop structure that can bewrapped around at least a portion of an inflatable body. The couplingbus according to a system, apparatus and method herein can be configuredto wrap around, or otherwise encircle, at least partially a portion ofan inflatable body.

In an example, the plurality of sensing elements can include one or moreof multiple sensor types, such as but not limited to, impedance sensors(including bipole electrodes), lateral strain sensors, temperaturesensors, intracardiac electrogram (EGM) sensors, light-emitting diodes(LEDs), including micro-LEDs, transistors (including switches),multiplexors, recording electrodes, radiofrequency (RF) electrodes(including RF ablation electrodes), temperature sensors, and/or contactsensors (including impedance-based contact sensors).

In an example, the plurality of sensing elements can includecombinations of different sensor types. In an example, the plurality ofsensing elements can include components such as pacing electrodes, EGMelectrodes, and bipolar electrodes. In another example, the plurality ofsensing elements can include components such as impedance electrodes andcontact sensing electrodes. In another example, the plurality of sensingelements can include power control components such as components thatcan perform ablation. In another example, the plurality of sensingelements can include active components such as components that canprovide for local signal amplification, e.g., for buffering or toprovide signal gain. In any example where the sensing elements includeactive components, the activation of the active component and themeasurements from the active component can be multiplexed.

In any example according to the principles described herein, the sensingelements, including electrodes, can be formed as conformal components,to conform to a shape and/or movement of a surface over which they aredisposed, including in flexibility and/or stretchability.

In an example, the sensing elements can be coupled to the coupling bususing at least one flexible connector. In an example, each sensingelement can be coupled to the coupling bus using a respective flexibleconnector. In another example, two or more of the sensing elements canbe coupled to the coupling bus by a single flexible connector.

Another example system, method and apparatus described herein that canbe used for medical diagnosis and/or treatment includes a flexiblesubstrate that forms an expandable body and a plurality of sensingelements disposed on the flexible substrate. The plurality of sensingelements can be disposed about the expandable body such that the sensingelements are disposed at areas of minimal strain of the expandable bodywhen in an unexpanded state.

Methods for fabricating an apparatus for medical diagnosis and/ortreatment are also described. An example method includes providing acoupling bus that is coupled to a plurality of sensing elements,disposing the coupling bus about a region of an inflatable body, anddisposing the plurality of sensing elements about a portion of acircumference of the inflatable body such that the sensor elements aredisposed at areas of minimal curvature of the inflatable body.

In various examples, the coupling bus can be disposed near a mid-portionof an inflatable body, for examples, near an equator of an inflatablebody. In other examples, the coupling bus can be disposed at a positionaway from the mid-portion of the inflatable body, for example, near adistal portion of the inflatable body. Regardless of the location of thecoupling bus relative to the inflatable body, the stretchable electronicsystem can be configured such that the sensing elements are positionedat regions of minimal curvature of the inflatable body in the deflatedstate according to the principles described herein.

An example method for fabricating an apparatus for medical diagnosisand/or treatment can include extracting the coupling bus and theplurality of sensing elements from a carrier substrate prior todisposing the coupling bus about the region of the inflatable body. Inan example method, disposing the coupling bus about the region of theinflatable body can include applying the coupling bus using adissolvable tape backing.

According to the principles described herein, a stretchable electronicsystem is also provided. The stretchable electronic system includes atleast one flexible annular interconnect and a plurality of electrodescoupled to the at least one flexible annular interconnect. The at leastone flexible interconnect can be configured similarly to the couplingbus described above, including being formed from similar materials orcombinations of materials, in similar shapes, and/or with similarelectrical and/or mechanical properties.

In an example, the plurality of electrodes elements can include one ormore of bipole electrodes, intracardiac electrogram (EGM) electrodes,recording electrodes, and radiofrequency (RF) electrodes (including RFablation electrodes).

In an example, the at least one flexible annular interconnect has afirst radius and each electrode in the first plurality of electrodes iscoupled to the at least one flexible annular interconnect via arespective flexible connector extending from the annular interconnectsuch that the first plurality of electrodes are positioned at a secondradius distinct from the first radius. The second radius can be greaterthan or less than the first radius.

In another example, the at least one flexible annular interconnect caninclude a second plurality of electrodes coupled to the at least oneflexible annular interconnect, each electrode in the second plurality ofelectrodes coupled to the at least one flexible annular interconnect viaa flexible connector extending from the annular interconnect such thatthe second plurality of electrodes are positioned at a third radius,distinct from the first and second radii. The third radius can begreater than the second radius.

In an example, the stretchable electronic system can include a flexiblesubstrate forming an inflatable body, the at least one flexible annularinterconnect and the first plurality of electrodes coupled to aperipheral portion of the flexible substrate. In an example, the atleast one flexible annular interconnect can include at least oneintermediate bus to electronically connect each electrode with anelectrical source. The at least one flexible annular interconnect can beconfigured in a serpentine morphology. In an example, the stretchableelectronic can further include a flexible substrate forming aninflatable body coupled to the at least one flexible annularinterconnect.

In an example, any system or apparatus according to the principlesdescribed herein may be entirely or at least partially encapsulated byan encapsulating material, such as a polymer material (including any ofthe polymer materials described herein). An encapsulating material canbe any material that can be used to laminate, planarize, or encase atleast one component of a system or apparatus described herein, includingany electronic or other type of component. For example, a method offabricating any system or apparatus according to the principlesdescribed herein can further include encapsulating the system orapparatus. In an example, an encapsulating material can be disposedover, or otherwise applied to, an apparatus that includes the flexiblesubstrate forming the inflatable body and the plurality of sensingelements disposed on the flexible substrate, or a stretchable electronicsystem that includes a flexible annular interconnect and a plurality ofelectrodes coupled to the flexible annular interconnect, where thestretchable electronic system is disposed on an inflatable body. Invarious examples, an encapsulating material can be disposed over, orotherwise applied to, solely to the plurality of sensing elements, thecoupling bus, and/or the stretchable electronic system that includes theflexible annular interconnect and the plurality of electrodes. In anexample, a polyurethane can be used as the encapsulating material. Inanother example, the encapsulating material can be the same material asthe material for the flexible substrate. Encapsulating any portion ofthe systems or apparatus described herein can be useful to enhance themechanical stability and robustness of the system or apparatus, or tomaintain electronic performance of the electronic components of thesystem or apparatus against a stress or strain applied to the system orapparatus during use.

In an example, any of the systems or apparatus according to theprinciples herein can be disposed on the inflatable body such that afunctional layer of the system or apparatus lies at a neutral mechanicalplane (NMP) or neutral mechanical surface (NMS) of the system orapparatus. The NMP or NMS lies at the position through the thickness ofthe device layers for the system or apparatus where any applied strainsare minimized or substantially zero. In an example, the functional layerof a system or apparatus according to the principles described hereinincludes the plurality of sensing elements, the coupling bus, and/or thestretchable electronic system that includes the flexible annularinterconnect and the plurality of electrodes.

The location of the NMP or NMS can be changed relative to the layerstructure of the system or apparatus through introduction of materialsthat aid in strain isolation in various layers of the system orapparatus. In various examples, polymer materials described herein canbe introduced to serve as strain isolation materials. For example, theencapsulating material described hereinabove can be used to position theNMP or NMS, e.g., by varying the encapsulating material type and/orlayer thickness. For example, the thickness of encapsulating materialdisposed over the functional layers described herein may be modified(i.e., decreased or increased) to depress the functional layer relativeto the overall system or apparatus thickness, which can vary theposition of the NMP or NMS relative to the functional layer. In anotherexample, the type of encapsulating, including any differences in theelastic (Young's) modulus of the encapsulating material.

In another example, at least a partial intermediate layer of a materialcapable of providing strain isolation can be disposed between thefunctional layer and the flexible substrate to position the NMP or NMSrelative to the functional layer. In an example, the intermediate layercan be formed from any of the polymer materials described herein,aerogel materials or any other material with applicable elasticmechanical properties.

Based on the principles described herein, the NMP or NMS can bepositioned proximate to, coincident with or adjacent to a layer of thesystem or apparatus that includes the strain-sensitive component, suchas but not limited to the functional layer. The layer can be considered“strain-sensitive” if it is prone to fractures or its performance can beotherwise impaired in response to a level of applied strain. In anexample where the NMP or NMS is proximate to a strain-sensitivecomponent rather than coincident with it, the position of the NMP or NMSmay still provide a mechanical benefit to the strain-sensitivecomponent, such as substantially lowering the strain that wouldotherwise be exerted on the strain-sensitive component in the absence ofstrain isolation layers. In various examples, the NMS or NMP layer isconsidered proximate to the strain-sensitive component that provides atleast 10%, 20%, 50% or 75% reduction in strain in the strain-sensitivecomponent for a given applied strain, e.g., where the inflatable body isinflated.

In various examples, the encapsulating material and/or the intermediatelayer material may be disposed at positions coincident with thestrain-sensitive component, including in the functional layer. Forexample, portions of the encapsulating material and/or the intermediatelayer material may be interspersed with the strain-sensitive component,including at positions within the functional layer.

In an example, a system, apparatus and method herein can be used todetect and/or quantify an amount of contact between an inflatable bodyand a tissue lumen. The locations and/or degree of contact between theinflatable body and the tissue lumen can be determined based on ameasurement of one or more of the sensing elements and/or the electrodesdescribed herein. In an example, the stretchable electronic systemdescribed herein can be used to determine a location and/or degree ofcontact between a tissue lumen and an inflatable body on which thestretchable electronic system is disposed.

As a non-limiting example, a system, apparatus and method herein can beused to detect and/or quantify an amount of contact between aninflatable body and a tissue lumen at different positions of theinflatable body relative to the tissue lumen. In an example, the system,apparatus and method include detecting a degree of contact betweenselect sensing elements or electrodes disposed on the inflatable bodyand the tissue lumen, and re-positioning the inflatable body to achievea desired degree of contact between the inflatable body and the tissuelumen. As a non-limiting example, the degree of contact between theinflatable body and a tissue lumen can be used to determine suitabilityof conditions for administering a therapy, or to determine a degree ofocclusion, or to reduce or eliminate the occlusion, including a blockageor closing of a blood vessel or hollow portion of an organ. The system,apparatus and method can be based on an apparatus that includes theflexible substrate forming the inflatable body and the plurality ofsensing elements disposed on the flexible substrate, or a stretchableelectronic system that includes a flexible annular interconnect and aplurality of electrodes coupled to the flexible annular interconnect,where the stretchable electronic system is disposed on an inflatablebody.

In an example, a system, apparatus and method herein can be used toadminister a type of therapy to tissue during a medical diagnosis and/ortreatment. The system, apparatus and method can be based on an apparatusthat includes the flexible substrate forming the inflatable body and theplurality of sensing elements disposed on the flexible substrate, or astretchable electronic system that includes a flexible annularinterconnect and a plurality of electrodes coupled to the flexibleannular interconnect, where the stretchable electronic system isdisposed on an inflatable body. For example, any of the inflatablebodies described herein may be disposed near a distal portion of acatheter, and a type of therapy may be introduced to a region of tissueduring the medical diagnosis and/or treatment. In an example, the typeof therapy may be introduced through a shaft of the catheter. In anexample, the therapy may be an ablative therapy and/or a drugadministration. Non-limiting examples of ablative therapy includecryo-ablation, laser ablation, and high intensity ultrasound.

An example method of performing a medical diagnosis and/or treatment ona tissue includes disposing in proximity to the tissue an apparatus thatincludes a flexible substrate forming an inflatable body, a couplingbus, and a plurality of sensing elements that are coupled to thecoupling bus. The one or more sensing elements of the plurality ofsensing elements include contact sensors. The coupling bus is disposednear a distal end of the inflatable substrate, and the plurality ofsensing elements are disposed about the inflatable body such that thesensing elements are disposed at areas of minimal curvature of theinflatable body. The method includes recording a measurement of at leastone sensing element of the plurality of sensing elements. Themeasurement provides an indication of a state of a portion of thetissue.

In an example, the measurement can be used to provide an indication of adisease state of the portion of the tissue. In another example, themeasurement can be used to provide an indication of a contact state ofthe portion of the tissue with the at least one sensing element of theplurality of sensing elements.

An example instrument and user interface is also described herein thatcan be used to display a representation of measurements of a pluralityof sensing elements or electrodes that are positioned proximate to atissue lumen. In an example, a instrument and user interface describedherein also can be used for mapping contact between a plurality ofsensing elements or electrodes with a tissue lumen. The measurement ormapping data can be used to provide a representation of a degree ofcontact between an inflatable body supporting the plurality of sensingelements or electrodes and the tissue lumen. An example instrumentand/or user interface can be used with any of the example systems,methods or apparatus described herein.

Example apparatus are also described for displaying a representation ofmeasurements of a plurality of sensing elements disposed about at leasta portion of a circumference of an inflatable body during a medicaldiagnosis and/or treatment of a tissue. In this example, the displayapparatus includes a display, a memory storing machine-readableinstructions, and one or more processor units to execute themachine-readable instructions. Execution of the machine-readableinstructions causes the display to display the representation of themeasurements. The representation includes a plurality of firstindicators and a plurality of second indicators. Each first indicatorcorresponds to a sensing element of the plurality of sensing elementsthat measures a signal below a threshold value. Each second indicatorcorresponding to a sensing element of the plurality of sensing elementsthat measures a signal above the threshold value.

In an example, a measurement below the threshold value can be used as anindication that the corresponding sensing element of the plurality ofsensing elements is not in contact with the tissue.

In an example, a measurement above the threshold value can be used as anindication that at least a portion of the corresponding sensing elementof the plurality of sensing elements is in contact with the tissue.

In an example, a measurement below a first threshold value can be usedto indicate a state of “no contact” or “no measurement” for a sensingelement. In another example, a measurement above a second thresholdvalue can be used to indicate a state of “contact” or “measurement” fora sensing element. In another example, a measurement between the firstthreshold value and the second threshold value can be used to indicate astate of “poor contact” or “poor measurement” for a sensing element.

An example apparatus is also described for displaying a representationof measurements of a plurality of sensing elements disposed about atleast a portion of a circumference of an inflatable body during amedical diagnosis and/or treatment of a tissue. The display apparatusincludes a display, a memory storing machine-readable instructions, andone or more processor units to execute the machine-readableinstructions. Execution of the machine-readable instructions causes thedisplay to display the representation of the measurements. Therepresentation can include a plurality of first spatial representationsand a plurality of second spatial representations. Each first spatialrepresentation corresponds to a sensing element of the plurality ofsensing elements that is disposed at a first latitude of the inflatablebody. The latitude can be specified relative to the distal end of theinflatable body. Each second spatial representation corresponds to asensing element of the plurality of sensing elements that is disposed ata second latitude of the inflatable body that is different from thefirst latitude,

In an example, each of the first spatial representations or each of thesecond spatial representations displays a first indication if thecorresponding sensing element measures a signal above a threshold value.In another example, each of the first spatial representations or each ofthe second spatial representations displays a second indication if thecorresponding sensing element measures a signal below a threshold value.

In an example, a system described herein can be used for mapping contactwith a surface. The system includes an inflatable body, plurality ofelectrodes coupled to the inflatable body, an electronic displayelectrically coupled to the plurality of electrodes. The electronicdisplay provides a visual reproduction of the spatial location of theplurality of electrodes on the inflatable body. The electronic displayalso changes a visual attribute of an electrode in the plurality ofelectrodes in response to a change in an electrical signal produced bythe electrode, where the change in the electrical signal can be used toidentify a contact condition of the electrode with respect to thesurface.

In an example, the visual attribute can be a binary representation or aquantitative representation.

In another example, a stretchable electronic system is described thatincludes a flexible interconnect, and a plurality of impedance basedelectrode pairs coupled to the flexible interconnect. The electrodepairs are configured to measure impedance between two electrodes of theelectrode pair.

In an example, a method of manufacturing a contact mapping ballooncatheter is also described. The example method includes identifyingregions of maximum curvature on the balloon of the balloon catheter whenthe balloon is in a deflated state, and coupling a plurality ofelectrodes to the balloon such that the plurality of electrodes arepositioned outside of the regions of maximum curvature.

The present disclosure also describes various non-limiting exampleimplementations of the stretchable electronic systems, methods andapparatus described herein. In an example, the example systems describedherein relate to various stretchable electronic systems and apparatusthat couple a catheter that includes an inflatable body with conformalelectronics to detect (and in some examples, quantify) an amount ofcontact between the inflatable body and a tissue lumen. The locationsand/or degree of contact between the inflatable body and the tissuelumen can be determined based on a measurement of one or more componentsof the conformal electronic system and the tissue lumen.

In an example, the catheter can be, but is not limited to, a ballooncatheter. In an example, the systems and apparatus described herein canbe implemented to guide a user (e.g., a clinician) in the delivery ofablation therapy to the lumen of a subject.

For example, the tissue can be cardiac tissue, and the lumen can be thepulmonary veins of a subject.

In a non-limiting example, the ablation therapy can be performed inconnection with the treatment of atrial fibrillation. Balloon catheters,including those configured for cryoablation, and may be used to treatpatients afflicted with atrial fibrillation. The balloon may be deployedand positioned at the pulmonary vein, and refrigerant may be deliveredthereby for cryotherapy through pulmonary vein isolation. To increaseefficacy of cryotherapy, the pulmonary veins may be occluded tosubstantially reduce the heat sink resulting from blood flow. A degreeof occlusion during cryotherapy may be assessed by injecting contrastmedia through the catheter's central lumen while simultaneously usingx-ray imaging to obtain information on the balloon-tissue interface.Example systems and apparatus described herein can be implemented forocclusion assessment, assessment of other medical conditions, and/orassessment of treatment progress, without the employment of contrastmedia and/or x-ray imaging.

The systems disclosed herein provide sensing feedback to the physicianon the degree of contact between an inflatable body and with tissuethrough the integration of impedance-based contact sensors directly onthe surface of the inflatable body.

As described further herein, example results of in a live porcine modelsdemonstrates that systems, apparatus and methods according to theexamples herein can be implemented to provide real-time guidance to auser (such as a physician) during use as part of a medical diagnosisand/or treatment. For example, systems, apparatus and methods can beimplemented to guide a user on how to adjust the inflatable body toachieve optimal occlusion of a tissue lumen (including the pulmonaryvein). A medical diagnostic and/or treatment procedure performed usingsystems, apparatus and methods of assessing occlusion described hereinmay be completed without exposing a subject to x-rays.

The present disclosure describe example results that show the utility ofcontact sensing in connection with medical diagnostic and/or treatmentprocedures using an inflatable and/or expandable body, includingcryoballoon ablation procedures.

Example systems and apparatus disclosed herein permit integration ofcomponents, including one or more electrodes, photodiodes, thermistors,micro-LEDs, and/or force sensors, or arrays of electrodes, photodiodes,thermistors, micro-LEDs, and/or force sensors, which may be deployed onflexible substrates. The systems and apparatus according to theprinciples herein can have a wide range of applications in the medicaldevice industry.

In an example, the sensing elements describe herein can include one ormore impedance-based contact sensors. In an application where a system,method or apparatus herein can be used to assess occlusion of a lumen,such as but not limited to an artery or a vein (including the pulmonaryvein). The work done in connection with these developments demonstrateexamples of a novel and practical approach for integrating conformalsensors and associated circuitry on an inflatable surface, including theballoon of a cryoablation balloon and other related medical devices.

An example therapy based on cryothermal energy represents an alternativeablation therapy to radio frequency (RF) energy for treating certainconditions, including cardiac arrhythmias. A cryoballoon system iscapable of delivering cryothermal energy through the transition ofnitrous oxide from liquid to gaseous phase. In this exampleimplementation, the transition of nitrous oxide from liquid to gaseousphase may be caused by an increase in pressure and a concomitantdecrease in temperature to −50° C. during the cryoablative procedure.The pulmonary vein ostium may be the structural target for ablation inparoxysmal AF patients. Achieving occlusion near the antrum of thepulmonary veins assists with achieving effective lesion formation withcryoballoons.

Contiguous, permanent lesions may be formed when the pulmonary veins areall circumferentially occluded by the cryoballoon. Blood flow due tosmall gaps between the balloon surface and a PV can cause local heatingduring cryoablation and could give rise to poor lesion formation. Toassess good occlusion, contrast dye may be injected through theguide-wire lumen and x-ray imaging may be used to visualize the flow ofdye passing along the balloon. The limitations of contrast dye injectioninclude poor image resolution to identify the exact location of theleaks in 3D space. Moreover, exposure to x-ray and ionizable contrastagents pose health risks to patients.

Examples of inflatable bodies are described herein relative to a type ofballoon catheter. However, the inflatable bodies applicable to thesystems, methods and apparatus herein as not so limited. It is to beunderstood that the principles herein apply to any type of inflatablebody (including an expandable body) on which stretchable electronicsystems described herein can be disposed.

FIG. 1 illustrates an example use of a system or apparatus herein for anincomplete occlusion of the tissue lumen 102 (e.g., ostium or pulmonaryvein) by an inflatable body (here it is catheter balloon 104) positionednear a distal end of a catheter, according to the principles describedherein. The example catheter balloon 104 shown in FIG. 1 has an “onion”shape described herein. The example catheter of FIG. 1 includes a shaft106. In an example, an ablative therapy can be introduced through shaft106. According to the principles herein, the plurality of sensingelements, the coupling bus, and/or the stretchable electronic systemthat includes the flexible annular interconnect and the plurality ofelectrodes can be disposed about the catheter balloon 104.

The plurality of sensing elements and/or the plurality of electrodesdescribed herein can be formed as sets of nanomembrane sensors andconformal electronics that can be used to perform a medical diagnosisand/or treatment as described herein. That is, the plurality of sensingelements and/or the plurality of electrodes described herein can bedisposed on the inflatable body (here catheter balloon 104 of FIG. 1)without substantially changing the mechanics and/or thermal profiles ofthe inflatable body.

In an example, the creation and implementation of highly conformalarrays of impedance-based contact sensors on balloon catheters aredescribed herein. Various examples of the systems herein include arraysof bipolar electrodes that are configured in a circumferentialorientation on the balloon surface. The use of sensor arrays on aninflatable body as described herein can be used to provide an insightinto localized mechanical interactions of the inflatable body andtissue, which can be poorly visualized with point sensing techniques. Asystem according to the principles herein can provide for highsensitivity contact sensing and provide insight into occlusion, thermalinteractions, and gap localization on the inflatable body (e.g., acryoballoon).

A pressure sensor that measures pulmonary vein pressure can beintroduced into a lumen prior to and following occlusion. Changes inpressure caused by occlusion can be assessed. This approach may notfacilitate assessing localized activity at different quadrants of theinflatable body (e.g., the catheter balloon) that align with the anatomyof the lumen.

The systems, methods and apparatus described herein provide designstrategies and fabrication techniques to achieve high performancestretchable electronics systems that are also flexible and that can beseamlessly integrated with inflatable bodies. The stretchableelectronics systems can include the plurality of sensing elements, thecoupling bus, the flexible annular interconnect and/or the plurality ofelectrodes. The stretchable electronics systems can be fabricated usinginorganic semiconductor processes.

In an example, the sensing elements, the coupling bus, and/or thestretchable electronic system that includes the flexible annularinterconnect and the plurality of electrodes may be fabricated on arigid and/or brittle substrate and then applied to the surface of theinflatable body. That is, various forms of high performance electronicsmay be fabricated on the rigid and brittle surfaces of semiconductorwafers or metallic wires in formats that are inherently low density maybe incompatible with establishing intimate physical coupling with thecomplex topologies of the atria and ventricles due to their rigidity.Various electronic systems may be further limited by their inability tooffer simple modes of functionality that do not allow real-time mappingover multiple sensor nodes. The systems, methods and apparatus describedherein provide technology to integrate thin, conformal arrays of sensoryelectronics on inflatable bodies, including deformable substrates suchas silicone or polyurethane balloon skins. The integrated systems andapparatus described herein permit electrical, thermal, and chemicalsensing components to be implemented on the surface of inflatablebodies.

In an example, the sensing elements, the coupling bus, and/or thestretchable electronic system that includes the flexible annularinterconnect and the plurality of electrodes can be formed using theultrathin designs of inorganic nanomaterials. These ultrathin designspermit implementation of flexible electronics over very small bendingradii, for example less than 100 microns. However, extreme bending andstretching conditions may induce greater strains or fractures in amaterial, such as in instances where these electronics interface withsoft tissue lumen (including soft tissues of the heart). For example,electronics on the heart can undergo large strains up to 10-20% or more.Sensors and electrodes on inflatable bodies for minimally invasiveprocedures may be subjected to even higher mechanical strain, exceeding100% strains in some instances. To alleviate the strains induced inthese situations, various forms of flexible nanomaterials may beimplemented, and may include serpentine layouts or buckled structures.FIGS. 2A-2C show scanning electron microscope images and correspondingfinite element modeling (FEM) results (inset) of stretchablenanomaterials/devices with different stretchable designs. FIG. 2A showsa 2D herringbone structure 200 that can be used to form interconnect.When the substrate of the herringbone structure 200 is stretched, theherringbone structure flattens to accommodate the stretching. FIGS. 2Band 2C show alternative structures that include selectively bondeddevice island regions with interconnects that are coupled to the deviceislands, and physically separated from the substrate at regions betweenthe device islands. Such interconnects can further enhance stretching.The interconnect structures of FIG. 2B appear as non-co-planar pop-upinterconnect structures 230, also referred to as buckled structures. Theinterconnect structures of FIG. 2C appear as serpentine interconnectstructures 270.

Stretchability of over 200% of the stretchable electronics systems maybe accomplished with non-coplanar serpentine-shaped interconnects.Device islands or electrodes may be coupled to a flexible substrate ofan inflatable body via covalent bonding. Serpentine interconnects may beloosely coupled through van der Waals forces. Therefore, subjecting thesubstrate to deformation may cause the metal interconnects, such as butnot limited to the serpentine interconnects, to detach from theunderlying substrate thereby relieving stress from the device islands.As a result, the maximum principal strain exerted on the interconnectscan be reduced by two orders of magnitude compared to the strain appliedto the underlying substrate.

FIGS. 3A and B illustrate an example of a stretchable electronic system300 that includes a coupling bus 302 and a number of sensing elements304. The stretchable electronic structure 300 can be coupled to aninflatable body according to the principles described herein. As shownin FIG. 3A, the sensing elements can be configured to include bipoleelectrodes 306. In the example configuration illustrated in FIG. 3A,there are 10 bipolar electrodes. However, other examples can includemore or fewer sensing elements 304. In the example of FIGS. 3A and 3B,the sensing elements are formed with the bipole electrodes 306 disposedon and/or surrounded by pads 307. In an example, the pads are formedfrom a polymer, such as but not limited to a polyimide. Each sensingelement 304 is coupled to the coupling bus 302 via a couplinginterconnect 308.

In the example of FIG. 3A, the sensing elements include bipoleelectrodes 306 that have substantially a square shape and the pads 307have a shape that extends substantially beyond the bipole electrodes306. In other example, the bipole electrodes 306 can have rectangular,circular or other polygonal shape and the pads 907 may not extend beyondthe bipole electrodes 906.

FIG. 3B shows a wider view of the example stretchable electronic system300 of FIG. 3A, and shows the intermediate bus that can be used tocouple the sensing elements to a circuit to provide power to and/orcollect measurements from, e.g., the sensing elements 304. Theintermediate bus and coupling interconnect in this any other exampledescribed herein can be formed from any suitable conductive material,including conductive materials described hereinabove.

As shown in FIG. 3A, the coupling bus 302 may have a non-uniformdistribution about the loop structure. For example, portions of thecoupling bus 302 that lead into the intermediate bus 310 are thickerthan other portions of coupling bus 302.

FIGS. 4B-C show magnified views of portions of the example stretchableelectronic system 300 of FIGS. 3A, 3B and 4A. As shown in FIGS. 4B and4C, the intermediate bus 310 is thicker than the coupling interconnect308. FIG. 4C also shows the lines of conductive structures that form theintermediate bus 310 and the coupling interconnect 308. As also shown inFIG. 4B, the coupling bus 302 can be formed in a serpentine (undulating)geometry. As also shown in FIG. 4C, coupling bus 302 can includeconductive portions 302A and non-conductive portions 302B, which can beformed from the materials described hereinabove.

FIG. 5A illustrates an example of a stretchable electronic system 500that includes a coupling bus 502 and a number of sensing elements 504.FIGS. 5B-D show magnified views of portions of the example stretchableelectronic system 500 of FIG. 5A. The stretchable electronic structure500 can be coupled to an inflatable body according to the principlesdescribed herein. As shown in FIG. 5B, the sensing elements can beconfigured to include bipole electrodes 506. In the exampleconfiguration illustrated in FIG. 5A, there are 10 bipolar electrodes.However, other examples can include more or fewer sensing elements 504.In the example of FIGS. 5A and 5B, the sensing elements are formed withthe bipole electrodes 506 disposed on and/or surrounded by pads. In anexample, the pads are formed from a polymer, such as but not limited toa polyimide. Each sensing element 504 is coupled to the coupling bus 502via a coupling interconnect 508.

FIG. 5A shows the intermediate bus 510 that can be used to couple thesensing elements to a circuit to provide power to and/or collectmeasurements from, e.g., the sensing elements 504

FIG. 5B shows a magnified view of the example stretchable electronicsystem 500 of FIG. 5A, and shows the intermediate bus 510 and couplinginterconnect 508. The intermediate bus 510 and coupling interconnect 508in this any other example described herein can be formed from anysuitable conductive material, including conductive materials describedhereinabove.

As shown in FIG. 5A, the coupling bus 502 may have a substantiallyuniform distribution about the loop structure. For example, portions ofthe coupling bus 502 that lead into the intermediate bus 510 are ofsubstantially similar thickness as other portions of coupling bus 502.

FIGS. 5C-D show magnified views of portions of the example stretchableelectronic system 500. FIG. 5C also shows the lines of conductivestructures that form the intermediate bus 510 and the couplinginterconnect 508. As also shown in FIG. 5C, the coupling bus 502 can beformed in a serpentine (undulating) geometry. As also shown in FIGS. 5Cand 5D, coupling bus 502 can include conductive portions 502A andnon-conductive portions 502B, which can be formed from the materialsdescribed hereinabove.

FIG. 6 illustrates a pair of sensors (rectangles) 600 attached to anunderlying polyimide layer 602 (a polyimide pad). The polyimide layer inthis example may not be stretchable, thereby allowing the distanceseparating the pair sensors 600 to remain substantially constant evenduring inflation of the inflatable body. This substantially constant gapsize between the sensor pairs helps reducing signal fluctuations duringinflation deflation and deformations of the inflatable body.

FIG. 7 shows the stretchable electronic system according to theprinciples of FIGS. 3A-B, disposed on an inflatable body 720. In thisexample, the inflatable body 720 is a balloon catheter. FIG. 8 is amagnified view of the balloon catheter of FIG. 7. The stretchableelectronic system includes coupling bus 702, sensing elements 704, andcoupling interconnects 708 and intermediate bus 710. The sensing element704 includes bipole electrodes 706. To test the ability of contactsensors on a balloon to verify occlusion, an array 10 bipolar ofelectrodes is implemented on an inflatable body to evaluate contact withpulmonary vein tissue relative to that of blood. Impedance of tissue isapproximately 1.5-2× higher than that of blood. Therefore, in anexample, contact between the inflatable body and the sensing elementscan be determined based on impedance measurements using the bipoleelectrodes. Based on insight into the placement of the inflatable bodyof FIG. 7 in the pulmonary veins, it is determined that the distal poleof the balloon is most likely to contact tissue. Therefore, sensingelements can be strategically distributed about the inflatable body tobe near points of potential contact. In an example system, the pointsfor placement of the sensing elements can be determined as specificlatitudes or circumferences of the inflatable body.

In a non-limiting example where the inflatable body is an ARCTIC FRONT®Cryoballoon Catheter (available from Medtronic Inc, Minneapolis, Minn.)balloon, the sensing elements can be positioned at about the 15 mm andabout the 20 mm diameter portions of the cryoballoon (as described ingreater detail in FIGS. 12A-12C). In this non-limiting example, theradius (R_(A)) of the coupling bus 1206 is around 12 mm, a first set ofthe sensing elements extend from the coupling bus 1206 to fall along acircle of a radius (R_(B)) of about 10 mm, and a second set of thesensing elements extend from the coupling bus 1206 to fall along acircle of a radius (R_(C)) of about 7.5 mm. The density of sensingelements facilitate identification of spatial gaps in occlusion betweenthe inflatable body and target lumen.

FIGS. 9-11 illustrate additional examples of stretchable electronicsystem according to the principles described herein. While the examplesillustrated in FIGS. 3A-5D and 9-11 include 10 distributed sensingelements, other examples may be implemented that include more or fewersensing elements. The sensing elements may be distributed in a mannerdistinct from that illustrated in FIGS. 3A-5D and 9-11. In an example,the sensing elements are contact sensors.

FIG. 9A illustrates an example of a stretchable electronic system 900that includes a coupling bus 902 and a number of sensing elements 904.FIGS. 9B-D show magnified views of portions of the example stretchableelectronic system 900 of FIG. 9A. The stretchable electronic structure900 can be coupled to an inflatable body according to the principlesdescribed herein. As shown in FIG. 9B, the sensing elements can beconfigured to include bipole electrodes 906. In the exampleconfiguration illustrated in FIG. 9A, there are 10 bipolar electrodes.However, other examples can include more or fewer sensing elements 904.In the example of FIGS. 9A and 9B, the sensing elements are formed withthe bipole electrodes 906 disposed on and/or surrounded by pads 907. Themorphology of the pads of the system of FIGS. 9A-D are different fromthe pads of the pads of the system of FIGS. 3A-D. In addition, thedimension of the sensing elements 904 relative to the size of thecoupling bus 902 are smaller than those in the example of FIGS. 3A-C orFIGS. 5A-D. In an example, the pads are formed from a polymer, such asbut not limited to a polyimide. Each sensing element 904 is coupled tothe coupling bus 902 via a coupling interconnect 908.

In the example of FIG. 9B, the sensing elements include bipoleelectrodes 906 that have substantially a rectangular shape and the pads907 have a shape that encompasses the bipole electrodes 906. In otherexample, the bipole electrodes 906 can have square, circular or otherpolygonal shape, and the pads 907 can extend beyond the bipoleelectrodes 906.

FIG. 9A shows the intermediate bus 910 that can be used to couple thesensing elements to a circuit to provide power to and/or collectmeasurements from, e.g., the sensing elements 904

FIG. 9B shows a magnified view of the example stretchable electronicsystem 900 of FIG. 9A, and shows the intermediate bus 910 and couplinginterconnect 908. The intermediate bus 910 and coupling interconnect 908in this any other example described herein can be formed from anysuitable conductive material, including conductive materials describedhereinabove.

As shown in FIG. 9A, the coupling bus 902 may have a substantiallyuniform distribution about the loop structure. For example, portions ofthe coupling bus 902 that lead into the intermediate bus 910 are ofsubstantially similar thickness as other portions of coupling bus 902.

FIGS. 9C-D show magnified views of portions of the example stretchableelectronic system 900. FIG. 9C also shows the lines of conductivestructures that form the intermediate bus 910 and the couplinginterconnect 908. As also shown in FIG. 9C, the coupling bus 902 can beformed in a serpentine (undulating) geometry. As also shown in FIGS. 9Cand 9D, coupling bus 902 can include conductive portions 902A andnon-conductive portions 902B, which can be formed from the materialsdescribed hereinabove.

FIG. 10A illustrates an example of a stretchable electronic system 1000that includes a coupling bus 1002 and a number of sensing elements 1004.FIGS. 10B-D show magnified views of portions of the example stretchableelectronic system 1000 of FIG. 10A. The stretchable electronic structure1000 can be coupled to an inflatable body according to the principlesdescribed herein. As shown in FIG. 10B, the sensing elements can beconfigured to include bipole electrodes 1006. In the exampleconfiguration illustrated in FIG. 10A, there are 10 bipolar electrodes.However, other examples can include more or fewer sensing elements 1004.In the example of FIGS. 10A and 10B, the sensing elements are formedwith the bipole electrodes 1006 disposed on and/or surrounded by pads.The morphology of the pads of the system of FIGS. 10A-D are differentfrom the pads of the pads of the system of FIGS. 3A-D. In addition, thedimension of the sensing elements 1004 relative to the size of thecoupling bus 1002 are larger than those in the example of FIGS. 3A-C orFIGS. 5A-D. In an example, the pads are formed from a polymer, such asbut not limited to a polyimide. Each sensing element 1004 is coupled tothe coupling bus 1002 via a coupling interconnect 1008.

FIG. 10A shows the intermediate bus 1010 that can be used to couple thesensing elements to a circuit to provide power to and/or collectmeasurements from, e.g., the sensing elements 1004

FIG. 10B shows a magnified view of the example stretchable electronicsystem 1000 of FIG. 10A, and shows the intermediate bus 1010 andcoupling interconnect 1008. The intermediate bus 1010 and couplinginterconnect 1008 in this any other example described herein can beformed from any suitable conductive material, including conductivematerials described hereinabove.

As shown in FIG. 10A, the coupling bus 1002 may have a substantiallyuniform distribution about the loop structure. For example, portions ofthe coupling bus 1002 that lead into the intermediate bus 1010 are ofsubstantially similar thickness as other portions of coupling bus 1002.

FIGS. 10C-D show magnified views of portions of the example stretchableelectronic system 1000. FIG. 10C also shows the lines of conductivestructures that form the intermediate bus 1010 and the couplinginterconnect 1008. As also shown in FIG. 10C, the coupling bus 1002 canbe formed in a serpentine (undulating) geometry. As also shown in FIGS.10C and 10D, coupling bus 1002 can include conductive portions 1002A andnon-conductive portions 1002B, which can be formed from the materialsdescribed hereinabove.

In the example stretchable electronic system of FIGS. 3A-10D, thesensing elements are directed outwards from the coupling bus. For theseconfigurations, the size of the coupling bus may be configured such thatit is disposed near a distal portion of an inflatable body, and thesensing elements disposed nearer to mid-portion (for some inflatablebodies, an equator) of the inflatable body. FIGS. 7 and 8 illustrate anexample assembly, where the coupling bus 702 is disposed near a distalend of a balloon catheter 720, which the sensing elements 704 aredisposed closer to an equator of the balloon catheter 720. As also shownin FIG. 8, the sensing elements can be disposed at different radii ofthe catheter balloon such that the sensing elements are disposed atdifferent latitudes relative to the balloon catheter. In another exampleimplementation using the stretchable electronic system according to theprinciples of FIGS. 3A-5D and 9A-10D, the size of the coupling bus maybe configured such that it is disposed near a mid-portion (or equator)of an inflatable body, and the sensing elements are directed towards thecenter from the coupling bus. When an example stretchable electronicstructure according to this example is mounted on an inflatable body,the sensing elements would be directed closer to distal portions of theinflatable body.

FIG. 11A illustrates another example of a stretchable electronic system1100 that includes a coupling bus 1102 and a number of sensing elements1104. In this example, the sensing elements 1104 are directed towardsthe center of the coupling bus 1102. FIGS. 11B-D show magnified views ofportions of the example stretchable electronic system 1100 of FIG. 11A.The stretchable electronic structure 1100 can be coupled to aninflatable body according to the principles described herein. As shownin FIG. 11B, the sensing elements can be configured to include bipoleelectrodes 1106. In the example configuration illustrated in FIG. 11A,there are 10 bipolar electrodes. However, other examples can includemore or fewer sensing elements 1104. In the example of FIGS. 11A and11B, the sensing elements are formed with the bipole electrodes 1106disposed on and/or surrounded by pads. The morphology of the pads of thesystem of FIGS. 11A-D are different from the pads of the pads of thesystem of FIGS. 3A-D. In addition, the dimension of the sensing elements1104 relative to the size of the coupling bus 1102 are larger than thosein the example of FIGS. 3A-C or FIGS. 5A-D. In an example, the pads areformed from a polymer, such as but not limited to a polyimide. Eachsensing element 1104 is coupled to the coupling bus 1102 via a couplinginterconnect 1108.

FIG. 11A shows the intermediate bus 1110 that can be used to couple thesensing elements to a circuit to provide power to and/or collectmeasurements from, e.g., the sensing elements 1104

FIG. 11B shows a magnified view of the example stretchable electronicsystem 1100 of FIG. 11A, and shows the intermediate bus 1110 andcoupling interconnect 1108. The intermediate bus 1110 and couplinginterconnect 1108 in this any other example described herein can beformed from any suitable conductive material, including conductivematerials described hereinabove.

As shown in FIG. 11A, the coupling bus 1102 may have a substantiallyuniform distribution about the loop structure. For example, portions ofthe coupling bus 1102 that lead into the intermediate bus 1110 are ofsubstantially similar thickness as other portions of coupling bus 1102.

FIGS. 11C-D show magnified views of portions of the example stretchableelectronic system 1100. FIG. 11C also shows the lines of conductivestructures that form the intermediate bus 1110 and the couplinginterconnect 1108. As also shown in FIG. 11C, the coupling bus 1102 canbe formed in a serpentine (undulating) geometry. As also shown in FIGS.11C and 11D, coupling bus 1102 can include conductive portions 1102A andnon-conductive portions 1102B, which can be formed from the materialsdescribed hereinabove.

An interconnect having a serpentine structure as described herein allowsfor stretching and compression of the system, ensuring survival of thesensing elements during deployment through a sheath. In an exampleimplementation, the sensing elements can be each about 1 mm2 in totalarea, to achieve sufficient contact with tissue. These configurations ofthe stretchable electronic system also employ coupling buses or annularinterconnects at or near the distal end of the inflatable body. In theconfigurations provided in FIGS. 3A-5D and 9A-10D, the coupling buses orannular interconnects is positioned at smaller radius than the sensingelements. In the example configuration illustrated in FIGS. 11A-D, theserpentine ring is positioned at a larger radius than the sensors. Thecoupling buses or annular interconnects can be used as a landmark forsteady alignment during assembly of the coupling buses or annularinterconnects with the inflatable body. The configuration of FIGS. 4A-Cappeared to exhibit the greatest resistance to delamination and had asignificantly smaller profile and that can be easier to navigate througha sheath compared to the large circular ring incorporated in theconfiguration of FIGS. 11A-D.

FIGS. 12A-12C illustrate the assembly of an example stretchableelectronic system 1202 (shown in FIGS. 12A and 12B) with an inflatablebody 1204. In the example of FIG. 12C, of the stretchable electronicsystem 1202 is configured such that the coupling bus is disposed near anequator of inflatable body 1204, and the sensing elements 1206 aredirected towards closer to distal portions of the inflatable body 1204.The differing radii of extent of the sensing element are configured suchthat they fall at specified latitudes of the inflatable body 1204. Forexample, the stretchable electronic system can be configured (based onthe differing lengths or differing capacities for stretchability of theflexible interconnect structures 212) such that a given sensing element1206 is disposed at latitude L1 or latitude L2 of the inflatable body1204. FIG. 12C illustrates an assembly process for integrating astretchable electronic system that includes a substantially circularcoupling bus or annular interconnect with an inflatable body 1204. Asnoted herein, the substantially circular coupling bus or annularinterconnect facilitates alignment during integration of the flexibleelectronic components with the inflatable body 1204.

In an example, using a balloon catheter, the latitude L1 can bepositioned at a level of the balloon catheter with a circumference thatis about 65% of the circumference of the equator of the balloon, whilethe latitude L2 can be positioned at with a circumference that is about87% of the circumference of the equator. The latitude(s) of placement ofthe sensing elements of a stretchable electronic system on an inflatablebody can be determined based on an expected contact point between theinflatable body and a region of a tissue lumen. For example, as shown inFIG. 1A, portions of an inflatable body 104 may be expected tosubstantially contact portions of a tissue lumen 102. The position ofplacement of the sensing elements can be determined such that one ormore of the sensing elements are positioned proximate to the tissue whenthe inflatable body is deployed in the tissue lumen. The latitudes(e.g., L1, L2, etc) may be decided based on such expected positioning ofthe inflatable body relative to the tissue lumen.

FIGS. 13A-15B show a non-limiting example implementation of fabricationof a stretchable electronic system according to principles describedherein. In particular, FIGS. 13A-15B show example intermediate stages inthe fabrication of the example stretchable electronic system. FIGS.13A-B shows magnified views of the integrated components of the deviceof FIG. 13C, a stretchable electronic system according to the principlesdescribed herein. FIGS. 14A-14B show the result of a metallizationprocess (facilitated using masking technology) to provide the metallayer of the stretchable electronic system in accordance with disclosedexamples. FIG. 14A shows the contact pads at the end of the intermediatebus that facilitates electrical communication with an external powersource and/or integrated circuit. FIGS. 15A-15B show the application ofencapsulant layer over some portions of the stretchable electronicsystem in accordance with disclosed examples. In an example, theencapsulant layer may be formed from any of the polymer materialsdescribed herein, such as but not limited to a polyimide layer, apolyeurethane layer, FIG. 15A shows that the contact pads at the end ofthe intermediate bus may also be coated at some portions with anencapsulant layer.

As shown in the example of FIG. 16, a plurality of stretchableelectronic systems may be fabricated on a single wafer or othersubstrate, extracted and disposed on an inflatable body according to theprinciples described herein.

FIGS. 17A-17B illustrate examples of a stretchable electronic systemdisposed about an inflatable body such that the sensing elements 1704are positioned at two different latitudes. FIGS. 17A-B ALSO illustratethe inflation/deflation process of the inflatable body. As shown, theinflatable body can be configured such that small ridges 1702 can formon the inflatable body surface in a deflated state, facilitating forbetter folding of the inflatable body. According to the principlesherein, and as illustrated in FIG. 17A, the plurality of sensingelements can be disposed about the inflatable body such that the sensingelements are disposed at areas of minimal curvature of the inflatablebody in a deflated state (which includes a collapsed state). Theconformal sensors/electrodes are strategically and selectively disposedbetween the ridges 1702 at areas of minimal curvature in the deflatedstate, to minimize applied strain on the sensing elements. Uponinflation of the inflatable body, the sensing elements are deployed in astaggered fashion on the flexible surface of the inflatable body.

FIGS. 18A-18C illustrate an example where the inflatable body is aballoon catheter. FIGS. 18A and 18B shows the transitioning of theballoon catheter between an inflated state (FIG. 18A) and a deflatedstate (FIG. 18B). The example balloon catheter of FIGS. 18A-18C has an“onion” shape in the inflated state (a pear-shaped with a curvilinearmorphology). Such a balloon may be configured to deflate and to formapproximately an average of about five (5) clover-shaped folds. That is,the ridges 1802 in the deflated state extend into the points of theclover-shaped folds, and portions of the balloon between the ridges, therecesses 1804, are disposed closer to the catheter shaft when theballoon is in the deflated state.

The determination of the configuration of the sensing elements on thesurface of an inflatable body includes analysis of high and low strainregions of the inflatable body in the deflated state to determinelocations on the inflatable body to situate sensing elements so thatthey experience minimal stress and/or strain, as demonstrated further inconnection with FIGS. 17A-B and 18A-18C. Finite element analysis of thestress-strain profiles also enables mechanical optimization such thatthe sensing elements are located in the area of minimal curvature of theinflatable body, thereby minimizing failure modes during operation (forexample, when the inflatable body is being introduced into a tissuelumen prior to being deployed near a tissue region of interest).

FIG. 19 is a schematic of a folded section of an example ballooncatheter in a deflated state. When a balloon catheter is not pressurized(e.g., in the deflated state), the balloon may form a plurality offolds. FIG. 19 depicts one example of such folds with respect to thecatheter shaft. FIG. 19 also shows a mathematical function that can beused to model the curvature (Kmax) at any point on the fold of theexample balloon catheter is represented by the equation Kmax=1.05(8/ExI/)^1/3, where p is approximately atmospheric pressure, E is theYoung's modulus of the material of the balloon, and I is the moment ofinertia of the balloon catheter.

FIG. 20 shows a graph illustrating the different in computed strainalong a folded section of a deflated balloon. In the example of FIG. 20,the arc length from the left point of the balloon to the k=0 location iscomputed at about s=0.75 mm. The curvature at the left end of theballoon is computed at about 4940 m⁻¹ (the maximum of all computedcurvature values). The curvature of the balloon at the right end iscomputed at about 823 m⁻¹. As shown in FIG. 20, higher strain regionsand lower strain regions (including regions of substantially zerostrain) of the inflatable body can be determined. Based on the modelingof the curvature of the balloon in the deflated state, the region on thefold of minimal curvature for the balloon can be determined.

According to the principles herein, based on a model of the expected orpredicted folding behavior of an example inflatable body on deflation orcollapse, an example stretchable electronic system may be configured,fabricated and integrated with an inflatable body such that the sensingelements are disposed proximate to regions of minimal curvature of theinflatable body (when in a deflated state). For any example inflatablebody according to the principles described herein, the folding (orcollapsing) behavior of the inflatable body can be modeled or determinedbased on a number of training samples of the inflatable body, where apattern of average or most likely folding behavior is determined. Asillustrated in FIG. 20, higher strain regions and lower strain regions(including regions of substantially zero strain), including regions ofminimal curvature, of the inflatable body can be determined. Theflexible interconnect that lead from the sensing elements to thecoupling bus can be disposed on the inflatable body so that theytraverses the regions of maximal curvature.

FIG. 21 shows an example schematic diagram of a balloon catheterintegrated with a stretchable electronic system 2104 according to theprinciples herein. In the illustrated example, the sensing elements,such as the electrodes, are positioned on the distal portion of theballoon 2102. The stretchable electronic system 2102 is coated with apolyurethane encapsulant layer. The polyurethane coated balloon isimplemented with a catheter that includes a flexible printed circuitboard (PCB) interconnection 2106. In an example, the PCBinterconnections may be bonded to the catheter. The electrical leadsfrom the PCB interconnections may extend to a connecter housing, whichhousing may be disposed exterior to the catheter.

FIG. 22 shows a flow chart illustrating a non-limiting example processfor fabricating an stretchable electronic system and integrating thestretchable electronic system with an inflatable body. In this example,the sensing elements of the stretchable electronic system includecontact sensors. In block 2202, the stretchable electronic system arefabricated in an array are provided. In block 2204, the stretchableelectronic system are transferred to a carrier substrate. In thisexample, the carrier substrate is a carrier tape. In block 2206, thecontact sensors and flex ribbon are connected using conducting film(ACF) bonding. In block 2208, the carrier tape is removed and thestretchable electronic system is integrated with the catheter balloon,including sensing elements placement according to the principles herein,to the integrated system including the stretchable electronic system andthe inflatable body. In block 2210, the integrated system is coated withan encapsulant layer of polyurethane to provided a dip-molded system. Inblock 2212, the flex ribbon is attached along the catheter shaft usingan adhesive so that the flex ribbon is aligned along the catheter. Inblock 2214, a heat protection can be applied to the flex ribbon, e.g., aheat shrink protection, to insulate and protect the flex ribbon whilehaving little effect on the balloon profile. The heat protection can beapplied by guiding a heat shrink over the balloon along the catheter. Inblock 2216, wires can be connected to facilitate communication betweenthe stretchable electronic system and a data acquisition module toprovide the fully-integrated system 2218 for use.

FIGS. 23A and 23B are examples of the layers of a balloon and anintegrated electrode configuration implemented to position theelectrical components in a neutral mechanical plane. Nanomembranecontact sensor geometries are unique in the way they impart flexibilityto otherwise rigid and brittle materials. Impedance-based contactsensors can be microfabricated using a multi-layer process. The activesensor layer nanometers in thickness and located in the neutralmechanical plane. Subsequent stacks of polyimide and polyurethane filmsprovide encapsulating support to help prevent delamination failuremodes. Any suitable encapsulating nonconductive/conductive polymersaccording to the principles herein can be selectively coated over thesurface of the electrodes. This additional layer of polymer providesadditional mechanical protection against shear stresses. Alternatively,a few classes of sensors can be located on the PET balloon and coveredby the PU layer. The sensors may be completely shielded from abrasion inthis particular configuration. Temperature sensors, iLEDs and flowsensors can be employed in this way.

FIGS. 23A and 23B show example layer structures of the stretchableelectronic system on a flexible substrate of the inflatable body. Thelayer structures of both FIGS. 23A and 23B include at least oneintermediate layer disposed between the functional layer 2308, and 2508and the flexible substrate 2302, 2352. For example, layers 2304 and 2306can serve as intermediate layers for the structure of FIG. 23A.Similarly, layers 2354 and 2366 can serve as intermediate layers for thestructure of FIG. 23B. The layer structures of both FIGS. 23A and 23Balso include at least one encapsulant layer 2312, 2362 disposed abovethe functional layer 2308, 2508 and the flexible substrate 2302, 2352.Layers 2310 and 2360 can also serve as encapsulants for their respectivedevice structures. In these examples, each have a number of layers thatcan serve to provide for strain isolation and place the NMP or NMS(indicated by the “h”) proximate to or coincident with the functionallayers 2308, 2358. While the layers in FIGS. 23A-B is shown with examplelayer thicknesses, the structures according to the principles herein arenot so limited.

Non-limiting example results of computations of the amount of strainexperienced in several layers of the example device of FIG. 23A is shownin Table 1.

TABLE 1 Material Max strain (%) gold 0.06 PI 1.5 DYMAX ® 27.6Polyurethane 41

Portions of the functional layer of the system coincide with the planelabeled “gold”. As shown in Table 1, the maximum strain computed for thegold layer is around 0.06%, which is lower than the strain computed forany other layer.

FIG. 24 illustrates a flex ribbon connector 2402 that can be used forelectrically coupling a plurality of sensing elements disposed on aninflatable body with a remote source.

FIGS. 25 and 26 show example configurations of a stretchable electronicsystem with a coupling bus that has an open-loop structure that can bewrapped around at least a portion of an inflatable body.

FIG. 25 illustrates a T-shaped sensing elements configuration inaccordance with various electrode examples. The illustrated T-shapedconfiguration, may be suited for an inflatable body with a longitudinalsymmetry, including a cylindrical inflatable body or an oval inflatablebody.

FIG. 26 illustrates a T-shaped configuration including an interfacebetween a coupling bus (also referred to herein as a main bus) of the Tshaped sensing elements configuration and a flexible printed circuitboard (PCB) positioned on a catheter shaft.

With reference to the FIGS. 25 and 26, the “T-configuration” for thesensing elements arrangement includes multiple contact sensors situatedalong the horizontal top portion of the T-configuration. The sensingelements in this example are configured as contact sensors electricallyinterconnected by “serpentine” buses (serving as the flexibleinterconnects). The contact sensors and serpentine buses form respectiveflexible/stretchable “arms” that wrap around an outer surface of theinflatable body when inflated. In this example, the coupling bus isdisposed at or near the “equator” of the inflatable bus (i.e., atapproximately the middle of the inflatable body). The vertical portionof the T-configuration includes an elongated rectangular-shaped “mainbus” that is situated along a longitudinal axis of the balloon (so thatit is subject to a smaller degree of stretching upon inflation).

To facilitate conformality of a sensing apparatus according to variousexamples disclosed herein, the flexible substrate of a conformal sensingapparatus may be formed of a plastic material or an elastomericmaterial, including any of a wide variety of polymeric materials. Thebottom terminus of the “main bus” of the T-configuration is coupled to aflexible printed circuit board (“flex PCB”) disposed along the shaft ofthe catheter. As noted below, the interface between the bottom terminusof the main bus and the flex PCB includes various examples. Small wiresto carry signals “off-catheter” can be attached to the flex PCB viasolder connection.

In one implementation, each contact sensor is wired individually (i.e.,two conductors/sensor) such that a pair of wires are available“off-catheter” for each sensor. Working from “off-catheter” to thecontact sensors themselves, and considering an example involving fivecontact sensors, ten wires are soldered to the flex PCB, and the traceson the flex PCB are designed such that there is approximately a“one-finger distance” between respective solder points (to facilitateassembly by hand).

The interface between the main bus of the T-configuration and the flexPCB involves the mechanical and electrical coupling of 10 contact pairsvia a specially selected adhesive and contact layout. In thisnon-limiting example, the main bus includes 10 conductors electricallyinsulated from each other, and two of these conductors that areelectrically coupled to a central sensor situated at the intersection ofthe main bus and the horizontal top bar of the T-configuration.

Four conductors then travel down the serpentine bus to the left of thecentral sensor (for the two additional sensors to the left of thecentral sensor), and four conductors travel down the serpentine bus tothe right of the central sensor (for the two additional sensors to theright of the central sensor). The “outermost” portions of the serpentinebus on the far left and far right arms each carry two conductors for theoutermost left and right sensors.

FIG. 27 shows an example of a stretchable electronic system having a“T-configuration” of coupling bus and sensing elements disposed over aninflatable body, such as a catheter balloon.

FIG. 28 a schematic diagram the flex board, according to one example.

The flex PCB may be referred to as the flex connector, or the flexboard. FIG. 28 provides an overview of the top layer of the flex board,which mates with the stretchable electronic system on the balloon.

On the left are 10 exposed metal contact pads that interface directlywith Pi-Cr-Au via ECCOBOND® adhesive (anisotropic conductive paste;Henkel Corp.), and provide connection to the flexible T electrodes.

The staggered rectangles on the right are the solder bumps that matewith wires leading along the catheter. They are staggered such that thewires do not bundle together. Bundled wires would cause undesirableincrease in catheter shaft diameter.

For adhering the balloon electrodes/contact sensors, the balloon (madeof e.g., Polyurethane polymer) may be selectively coated with DYMAX® 204UV curable adhesive (Dymax Inc,) with a lateral spatial resolution of,for example, >25 gm.

Prior to UV exposure, the balloon is wrapped with a sensor array distalto the equator.

The assembly is then placed under UV light cycles to promote strongadhesion between surface of the balloon and the back-side surface of thesensor array. For example, the assembly can be exposed to UV light at 15second intervals for up to about 5 minutes. In another example, the UVlight is cycled at 30 second intervals.

Next, the water-soluble tape is dissolved away, and the surface of theassembly of the balloon and the sensor array is dried.

Mold polyurethane may then be sprayed onto the surface of the balloonwith predetermined thickness and configuration of top encapsulation.

Windows can be left open surrounding the electrodes so that they remainexposed for effective tissue contact.

Once the spray mold procedure is complete, UV cure/polymerizationfollows, creating an even coat of polymer on the balloon. This top layerof polymer provides further protection against shear forces and mayimpact durability of the balloon catheters/sensors assembly.

Clinicians may use x-ray to determine when the balloon is out of thesheath and inside the left or right atrium (i.e., positioned in aspecified contact with the tissue lumen). Some clinical protocols usex-ray even during the pre-ablation routine to determine the type ofcontact the catheter balloon has with the tissue.

An example integrated system according to the principles describedherein may be used to provide an indication of when the balloon exitsthe sheath and comes in contact with blood. The sensors providing inaccordance with disclosed examples permit identification of locationssuch as inside the heart and passed the sheath (prior to any sensingwithin the ostium).

The technology used in this flex connector is applicable to many otherapplications as well, and the flexible/stretchable materials makephysically and electrically robust connection to rigid components in asystem.

The following disclosure describes various challenges associated withmaking a reliable, robust connector for electrophysiology, and designconsiderations which may be applicable to address these challenges andother applications.

A reliable connection is desired between the sensing elements and theflex board. For example, the larger the contact area, the sturdier theconnection that can be made between the electrodes and the flex board.In one example, the area is constrained to about 2 mm in width (ydirection in FIG. 28) because of the catheter shaft dimension, as thisflex board is disposed inside a catheter shaft. In addition, increasingthe length too much can also make it difficult to align.

An adhesive may be used to make the electrical and physical contactbetween the flex board and the T electrodes. In one measurement, ACFtapes manufactured by 3M are used. Alternatively, ECCOBOND® can be used.Measurements can be run to optimize the area of bonding, temperature,and duration of adhesive application.

In some examples, the target contacts may be made sufficiently largeenough so that the electrodes may be manually assembled to the flexconnector. The contacts (shown on the left side of FIG. 28 aresufficiently wide to be visible by eye. Moreover, they are sufficientlyshort in the X direction such that small rotational errors in placingthe T electrodes may not cause a misconnection.

In an example, a large electrical contact area is desired but it can belimited by the width (y direction in FIG. 28) of the connector becauseit fits in a catheter. In addition, if the length of the total length ofall contacts (x direction in FIG. 28) is too long, rotational errors inplacement can misalign the far left and far right contacts. This is dueto that when the flex PCB is placed on the T electrodes, there is atendency for rotation.

The longer the x direction, the greater the arc as determined by theradius from the center to the far x edge multiplied by the angle. Thus,there is a balance of opposing goals. On one hand, it is desirable toimprove visibility and hand manufacture by making the pads bigger andlonger. On the other hand, increasing them too much adds rotationalerrors and a jig can then be used to keep the components from rotating.This trade-off can be determined by trial and error.

In an example according to the principles herein, the total electricalcontact area is roughly 6.3 mm×1 mm and includes of 10 individualcontacts. Increasing the area makes the electrical contact stronger. Tomaintain equal impedance for each of these electrical contacts, they aremade to be the same area.

In addition, since some limitations may be place on the number of layersof flex board, the electrodes are sized in such a way that traces can berouted. The contacts start out longer in the y direction on the left butbegin to switch to rectangles that are longer in the x direction as itmoves to the right. The same area is maintained in each case, not onlyto align impedance but also to maintain good contact.

Many contacts span longer in the y direction since this flex board goesinto a catheter. The majority of pressure on the flex board is at thenorth and south edges (staring down at the flexboard shown in FIG. 28).The catheter shaft can be viewed as “hugging” this flex board andbending the north and south edges. Thus, it is desirable to ensure thereis some amount of electrical contact in the middle region between thenorth and south of the flex board.

The flex board can be configured to have two (2) layers, as additionallayers may increase stiffness and may adversely affect the flexibilityof the catheter. In addition, it may exceed the catheter shaft sizelimit. Fewer layers of flex board can be used but still provide for theoptimal number of traces. In one example, a 2 mil polyimide base, a 1mil polyimide film insulation, and a 1 mil acrylic adhesive areincluded. Thinner materials can be adopted, although the cost may behigher.

Manufacture of a longer (e.g., 48″) and thin flex board may beassociated with high cost and low yield. Alternatively, a short flexboard (e.g., 6″) may be used, with longer wires.

The flex board can be made contact with the flexible sensing elements(including electrodes). In one example, the total length of the flexboard is about 6 inches. The right side of FIG. 28 shows the wirecontacts. By using wire for the majority of the catheter length, thecost can be reduced while maintaining a relatively thin size. This alsoimproves flex board yield.

The wire contacts can be made water-proof since this is anelectrophysiological application and the catheter is in the body. Thewires are soldered onto the wire contacts, and a protective material,such as but not limited to ECCOBOND® 45+Catalyst 15 (Emerson & Cuming,Randolph, Mass.) can be applied, e.g., to them to make them water proof.

This example flex board design shown in FIG. 28 has 10 electrodes. Thisdesign can scale by using two flex boards to increase to 20 channels.The number of channels on one flex board can be increased and additionalwire contacts added.

In some examples, a multiplexer is added to the flex board to reduce thenumber of traces on the flex board while allowing many channels. Asystem according to one example has a multiplexer on the balloon itselfto minimize the number of traces at the flex board.

FIG. 29 illustrates an example schematic plan for a flex board design.

FIG. 30 illustrates the bottom layer of the example flex board.

FIG. 31 illustrates a top layer of the example flex board.

FIG. 32 illustrates an encapsulation layer of the example flex board.

Vertical orientation of contact pads and traces can help maintain alow-diameter catheter shaft.

The contact pads can be optimized by making them wide in the Ydirection. The flex board bends across the shaft in the Y direction.Thus, largest forces occur at the furthest Y edges. Therefore, tomaintain good contact, spanning the entire Y may be desired. Increasingthe area is also a goal to improve electrical contact. The constraint isthe overall contact group size. In this example, it is roughly 2 mm in Yand 7 mm in X.

In one example process of manual bonding, the main bus and flex PCB arefirst manually aligned with a microscope; then a device is beingconstructed to perform alignment and heat curing; if contact pads do notoverlap or if they touch adjacent pads then the circuit may be shorted.

Suitable adhesives/epoxies for appropriate strength and flexibility usedto couple the main bus and the flex PCB may include ECCOBOND®, andHYSOL® (Henckel, Rocky Hill, Conn.) CE3126 snap curable anisotropicadhesive, the latter can be cured at 170° C. for 4 minutes to bond themain bus and flex PCB. Other suitable adhesives/epoxies may also beused.

The main bus can be made narrow (e.g., <1-2 mm) in order to achieve asmooth transition from the catheter shaft to the surface of the balloon.The more conductors, the more lateral width is added to the main bus.Fewer serpentine interconnects may be disposed along the main bus giventhe vertical orientation.

Because most of the strain occurs along the horizontal direction duringinflation, and not the vertical in most ellipsoidal and spheroidalballoons, an example configuration includes keeping the length of themain bus minimized (impedance low) and the width as narrow as possible.

The main bus can be made wavy to allow for stretching during ballooninflation/deflation. Alternatively, a straight main bus can be flexiblebut not stretchable. The wavy design can be used to place electrodesdistal on the balloon, as the main bus may travel over a greater ballooncurvature.

The sensors and serpentines can be microfabricated during the sameprocess of polymer and metal vapor deposition. They can be deposited insequential layers. The discrete sensors may be picked and placed ontothe underlying metal interconnect layers, thus forming a network ofmetal interconnections with discrete sensor units.

Anisotropic conductive films and a flip chip bonding tool can beemployed to make these connections. Alternatively, conductiveanisotropic epoxies, such as the ECCOBOND® 3126 resin, can be used.

Serpentine interconnects can have greater curvatures to allow for morestretching. The coupling busses and interconnects described herein cabbe formed of interconnects with a serpentine geometry. Optimal designscan be based on the balloon geometry, electrode placement, and foldingbehavior for inflation/deflation.

In one example, electrical “bipole” sensing elements are used to measureimpedance difference between blood and tissue of lumen's inner surfacethrough “current injection” and voltage measurement across bipole pair(at ˜kHz frequency operations for example).

Polyimide pads can be disposed underneath bipoles to prevent changes inseparation distance upon inflation. The polyimide pads under electrodescan be made slightly larger to accommodate an encapsulation layer aroundthe electrode border, minimizing delamination.

The degree of contact can be determined based on that greater amount ofpressure applied to tissue can give a higher impedance, and can showwhether the electrodes are in complete contact or partial contact(decreased impedance).

Tissue characterization can be realized using measurements of impedancechanges in healthy tissue as compared to damaged tissue. Electricalimpedance can also be used, post-ablation, to assess lesion depth. Auser interface allows visualization of contact in real time.

In one example, the contact sensing elements employ PSR (pressuresensitive rubbers), such as Piezo-electric conductive polymers. In someother examples, capacitive sensors can be employed, where blood or bodytissue results in different changes in the capacitance.

In some examples, temperature sensors are disposed on the balloonsurface. Changes in electrical impedance can also be based on localtemperature. The temperature sensors can provide real-time temperaturedata during cryoablation or RF ablation.

Monitoring tissue temperature can provide estimate of lesiondepth/quality. LEDs can be disposed on the balloon to provideillumination.

A “T”-configuration of individually-wired contact sensing elements andtheir electrical characteristics are described.

Balloon shapes from different manufactures may differ, and size,geometry, placement/orientation of sensor assembly can be customized ondifferent balloons. In one example, sensors can be placed distal onballoon for pulmonary vein isolation (PVI) monitoring. Different stretchbehavior may exist for balloon inflation/deflation. In one example, verysmall ridges exist on a Cryoballoon manufactured by a particularmanufacturer, which may experience more stretching between inflation anddeflation. The surface area of a deflated balloon may limit the size andnumber of electrodes. In one example, the electrodes are staggereddiagonally to fit more on a deflated balloon. The electrodes can spreadout into a line upon inflation.

In one example, the electrodes are staggered in two rows, or as verticallines on the balloon, as described in the related patent applications.

Modeling the behavior of respective sensors from the central sensor tothe outermost left and right sensors may be used to derivefrequency/impedance characteristics of these sensors. For example, theimpedance can be 2-3× larger for sensors on the edges compared to thecenter sensor. The impedances may not be symmetrical around the main busor matched, so long as they are below a threshold. Signal filters andgain adjustment can be used to amplify signal amplitudes. In oneexample, the T-shaped structure is symmetric and has known changes inimpedances. The overall variations in impedance are not significant toeffect signal analysis.

For PVI, a higher density of sensors may be used to determine a completeocclusion. The density of sensors may be limited by the number of wiresthat can fit in the flex PCB, the number of contact pads on the flexPCB, the size of main bus, etc.

A non-limiting example of integration of a stretchable electronic systemand an inflatable body can be implemented as follows.

Block 1. As illustrated in FIG. 33, water soluble tapes can be applied.Water-Soluble Wave Solder Tape 5414 (water soluble poly-vinyl alcoholbacking with synthetic adhesive) can be applied over the fabricatedsensing elements array on the silicon wafer. Horizontal strips can belaid first.

Block 2. As illustrated in FIG. 34, the electrode array is removed fromthe silicon wafer. The soluble tape and sensing elements array can beremoved from the wafer starting on one of the top corners of the “T”.The array can be transferred to a piece of flex metal, leaving thebottom portion with the flexboard connection hanging off the edge of themetal.

Block 3. As illustrated in FIG. 35, the tape can be applied to theflexboard connection. A piece of polyimide (PI) tape is affixed to theexposed soluble tape on the back side of the flexboard connection.

Block 4. As illustrated in FIG. 36, the flexboard connection is exposed.The soluble tape s removed from the region with the PI-tape, leaving theelectrode array affixed to the PI. The soluble tape is excised at the PIand flex metal junction. Exposing the exposed length of PI/soluble tapeto a water bath at ˜50° C. can cause the soluble tape in the region overthe PI tape to selectively dissolve.

Suitable materials other than water soluble tape may be used. Forexample, tapes with short adhesive life cycles can be used within afinite time window. Once the adhesive are reduced, the outcome can besimilar to when one applies water to the water-soluble tape.

Block 5. As illustrated in FIG. 37, the array is placed on glass. Forexample, a glass slide can be affixed behind the flex metal and PI stripusing PI tape. Large portions of the flexboard connection may be leftexposed.

Block 6. The glass slide can be affixed to a microscope stage so thatthe contact pads on the flexboard connection are clearly visible throughthe eyepiece.

Block 7. As illustrated in FIG. 38, the contact pads are coated withadhesive. A thin coat of HYSOL® ECCOBOND® CE3126 (a heat curableanisotropic adhesive) can be applied over the electrode contact pads onthe flexboard connection so that the pads are still be visible throughthe layer of ECCOBOND® adhesive.

Block 8. As illustrated in FIG. 39, the flex board is attached to theelectrode array. The flexboard can be aligned with the contact padsusing the microscope. A PI tape can be applied horizontally over theflexboard to hold it in place over the contact pads.

Block 9. Proper alignment between the flex board connections on theelectrode array and the flex board is verified. All contact pads shouldbe aligned and not in contact with adjacent pads or connections. Ifalignment is not correct, and the process of FIG. 39 can be repeated.

Block 10. The adhesive is cured, as illustrated in FIG. 40, at atemperature of about 170° C. Care should be taken not o shear theflexboard in any direction while the ECCOBOND® is going through thecuring process.

Block 11. It should be determined if the ECCOBOND® is fully cured, i.e.,there is not fluid movement about the flexboard. If the ECCOBOND® is notfully cured, block 10 can be repeated.

Block 12. The sensing elements array can be removed, as illustrated inFIG. 41. Excess soluble and PI tape can be removed from the edges of the“T” and flexboard to create a narrow outline around the electrode array.

Block 13. The flexboard is attached to the balloon catheter, asillustrated in FIG. 42. In this example, the array is applied while theballoon is fully deployed. An epoxy is applied to the catheter shaft, asclose to the balloon as possible. The neck of the T-shaped configurationis applied down the shaft of the catheter so that the “T” portion liesaround the equator of the balloon. In an alternative example, the flexboard can be adhered to the balloon catheter using PI tape, where the PItape is placed as close to the balloon as possible.

Block 14. The sensing elements array is removed. The soluble tape isremoved, with the array attached, from the flex metal and glass slide.The soluble tape remains on the catheter shaft.

Block 15. An adhesive is applied to the sensing elements array, asillustrated in FIG. 43. As the sensing elements array is separated fromthe balloon, a flexible bond adhesive can be applied, such as but notlimited to a 208CTHF Ultra LightWeld (sold from DYMAX®, flexible bondingadhesive) to the backside of the “T”. A small injector tip may be usedto apply the adhesive.

In an alternative example, DYMAX® bonding adhesive is applied to theballoon.

Block 16. Place the electrode array on the balloon surface, asillustrated in FIG. 44. The array is applied to the balloon, beginningnear the shaft and working towards the equator. The arms of the “T” arewrapped around the balloon, making sure that the electrodes are alignedaround the equator and that the soluble tape is completely flat aroundthe balloon.

Block 17. The adhesive is cured. The DYMAX® adhesive is cured at about630 mW/m². Each 5 mm² area can be exposed to UV light for about 15seconds.

In an alternative example, a low intensity UV chamber can be used forcuring. The integrated system can be slowly rotated in the presence ofthe low UV light for about 30 seconds. Contact with the UV light sourceor the UV chamber should be avoided. After curing, the DYMAX® should beallowed to dry.

Block 18. The soluble tape can be dissolved, as illustrated in FIG. 45.The balloon is placed in a water bath at room temperature to dissolvethe soluble tape on the surface of the balloon. Contact with theflexboard connection with the water bath should be avoided. Theintegrated arrays-balloon system can be dried at room temperature.

Block 19. Apply an additional encapsulation layer can be applied, suchas but not limited to a DYMAX® encapsulation layer. The encapsulationlayer ca be applied to cover the serpentine structures as well(including in the coupling bus and in the flexible interconnects). Thesensing elements pads may not be coated with an encapsulation layer.

Block 20. The additional encapsulation layer may be cured.

A non-limiting implementation is evaluated using a glass funnelapparatus to demonstrate feasibility. FIG. 46 shows a schematic exampleof a balloon catheter including integrating sensing elements coupledwith a data acquisition and graphical user interface. In a non-limitingexample, the sensing elements can be electrodes. A data acquisitionsystem is implemented to support the sensing element to provide userfeedback on the sensor sensitivity and speed. Once the sensing elementfabrication is completed, contact sensing is evaluated in a glass funnelapparatus to demonstrate feasibility. Taken together, the designs,fabrication strategies and feasibility measurements provide insight intothe optimal configuration of conformal sensors on the inflatable body(such as but not limited to a balloon catheter). The data acquisitionand user interface associated with the conformal sensing elementsprovide real time data on the behavior of different physicians andquantitative metrics on their occlusion technique. This information maybe viewed as a function of time and show occlusion success rates as theyrelate to procedure outcomes.

In an example implementation, the data acquisition system forimpedance-based contact sensing elements includes a National Instrumentsdata acquisition system, a data acquisition (DAQ) hardware/softwaremodule for data acquisition, and calibration references. Measurements ofthe calibration references can be used to determine threshold values foranalysis of the measurements, according to the principles describedherein. The excitation current from the current source passes throughtissue to generate a voltage, which may then be measured with a NationalInstruments PXI-6289 data acquisition card. LABVIEW® software (NationalInstruments Corporation, Austin, Tex.) can be used to control the outputcurrent and frequency of the excitation current. For the measurement,the excitation current may be set at 10 μA and measurements are taken at1 kHz and 10 kHz. One function of the DAQ can be to display real-timecontact data from the inflatable body in a manner that allows the userto interpret whether occlusion of the pulmonary vein has been achievedor not. In an example, a display separate from the data acquisitionsystem can be used. To achieve a data acquisition system with a simpleuser-interface, binary (semi-quantitative) and quantitative (bar plots)representations of changes in impedance are used to facilitatevisualization of an amount of contact across the sensors of an examplesystem. In the binary representation, a baseline threshold is set basedon the impedance measured in saline when the balloon sensors arefloating. The threshold is set to about 1.5× to follow the largerimpedance of tissue relative to that of blood. As a result, the balloonsensor nodes turned from gray to blue, denoting good contact (rise inimpedance of greater than about 1.5× relative to the baselineimpedance).

FIG. 47 shows an example circuit diagram of a unidirectional constantcurrent source used for impedance measurements data according toprinciples described herein.

FIG. 48 shows an example circuit diagram of a bidirectional, lowdistortion current source used for impedance measurements data accordingto principles described herein. FIG. 48 shows an example circuit diagramof 10-channel sensing elements (such as contact sensing elements array).A voltage can be measured across the same two terminals where constantcurrent is applied (˜3 kHz).

The circuits shown in FIG. 47 and FIG. 48 are voltage controlled currentsources. The current passes through either blood or tissue. Theresulting voltage may differ depending on whether it is the currentpassed through blood or tissue. Accordingly, the characteristicimpedance can differ and it can be determine if a balloon catheter is incontact with tissue or blood based on impedance measurements. In oneexample, a factor of two (2) difference in impedance can be measured.This difference can be sufficient for measurements during contact/nocontact cycles.

An example system, impedance Proto 1 shown in FIG. 47, is aunidirectional constant current source. It can be used to provide a highimpedance node to the tissue (referred to as “subject under test” SUT).The high impedance node allows for a controlled amount of current toexcite the tissue (SUT).

An example system, impedance Proto 2 shown in FIG. 48, is abidirectional, low distortion current source. It can be used to drivemultiple channels (in this example, 16 are shown). The output can bemultiplexed so one channel sees 10 μA at any given time, which followsthe IEC60601 safety guidelines. This can prevent cross-talk betweenchannels and also can create a level of safety because the circuitdelivers a known regulated amount of current to a particular channel ata given time.

Impedance Proto 2 of FIG. 48 can be used to keep both N and P outputtransistors biased so that it operates in the linear region. By steeringcurrent with the N transistor, the high frequency signal can be passedinto the MUX, which then passes it to 1 of 16 channels to the SUT. Inaddition, this output stage has high linearity, which is helpful whendriving the SUT at higher frequencies.

In addition to adhering to a current limit, both circuits aregalvanically isolated, using an isolating transformer for example, fromthe power mains.

The voltage measured across the SUT yields real and imaginary values.Both characteristics can be taken into account to discern between bloodand tissue. Analog and digital filtering can be applied to eliminatenoise artifacts that include 50/60 Hz line noise and electro-magneticinterference from other instruments in the operating room. A low passfilter can be employed to eliminate the high frequency noise.

FIG. 49 provides a series of screen shots of a graphical user interfacedemonstrating a variety of conditions simulated with a balloon catheterincluding integrated sensing electronics positioned in a glass heart.

The flex ribbon can be used to establish an interface with the sensingelements and a data acquisition system. The conformal sensing elementscan interface with an intermediate wires or flex ribbon in order totransmit data to a data acquisition system. To achieve thisinterconnection, flex ribbons can be used that have thin and narrowwidth profiles to transmit data along the slender catheter and out tothe data acquisition system console. Custom bonding can be used tocontrol pressure and temperature, set over a small range to achieve arobust electrically continuous interface. The devices can be routedalong the shaft. Heat shrink can be used as insulation to shield theflex ribbon connections from the fluid environment inside the body.

An impedance can be measured upon insertion and inflation of theinflatable balloon (in this example, a cryoballoon) within a lumen. Inthe example of FIG. 49, the cavity of a glass funnel (˜50 mm outerconical diameter) immersed in saline buffer solution (phosphate buffersolution) is used as a demonstration of a tissue lumen. The apparatusincludes a thermal regulator/circulation unit to maintain bodytemperature in the bath. FIG. 49 shows representative data fromconformal sensors nearby (no contact state) and in good contact with thefunnel. The funnel test shows impedance values on the order of 10-15×greater during contact state relative to impedance of floating catheterin saline. Although tissue impedances are significantly smaller thanthat of glass, this initial study validated the concept of embeddingcontact sensors on the inflatable body (such as the cryoballoons).

The measurements of conformal sensors are provided to a data acquisitionconsole to make measurements in an elastomeric phantom heart model. Acatheter (n=7) in a phantom heart model can be deployed coupled with a14F sheath access port. This initial study is used as a way to evaluateencapsulation polymers and durability of the conformal sensors on theballoon. Initial results with UV-curable polymer adhesives showedsignificant delamination upon entry into the phantom left atrium. Withusage, some delaminations of the serpentine buses and contact sensorpads may occur. In various examples, different types of polyurethaneencapsulants can be used to enhance the mechanical stability of theserpentine buses and contact sensor pads, promoting greater durabilitywhile preserving stretchability, transparency, and biocompatibility.

Use of an encapsulant according to the principles herein, in addition toenhancing delamination, reduced the thermal effects of having conformalsensors on the balloon during cryoablation and minimized the effect ofcryo-thermal cycling on performance of the sensing elements. The resultsdemonstrated minimal changes in thermocouple measurements forcryoballoons with embedded sensors relative to those without, indicatingthat the conformal sensors minimally act as thermal sinks Cryothermalcycling is conducted using an alcohol bath adjusted to −56° C.Cryoballoons with conformal sensors exposed to this temperature overmany cycles at 4-minute intervals. No changes are seen in sensor opticalcharacteristics and overall performance following this testing. Theseresults indicate that repeated exposure to cryoenergy does not affectthe performance of conformal sensors on the cryoballoon. Other catheterfeatures, including mechanical deflection, sheath deployment and shaftsize, are all examined to understand the impact of contact sensors onthe overall look/feel and performance of the cryoballoon with embeddedcontact sensors.

To establish a robust quantitative means of assessing occlusion, thechanges in impedance measured during cryoballoon occlusion in the rightsuperior PV (RSPV) can be assessed. The results provide, for the firsttime, a new way to assess occlusion while concurrently allowing thecollection of new data on the behavior and successes of individualcryoballoon operators. These behaviors are evaluated during occlusionprior to ablation and during cryoenergy injection.

The cryoballoon contact is measured using impedance in a tissue lumen oflive pigs by deploying inflatable bodies with contact sensors through a14F sheath into the left atrium. Tests show sensors can assess contactwith PV ostium immediately prior to cryoablation.

FIG. 50 provides a series of screen shots of a graphical user interfacedemonstrating a variety of contact conditions with a balloon catheterincluding integrated sensing electronics positioned in a tissue lumen ofa live pig.

Shifts in impedance caused by tissue contact are observed usingimpedance-based contact sensors. FIG. 50 shows results from a leftsuperior pulmonary vein of a pig heart whereby contact is achievedacross all active sensors and confirmed with injection of contrast dye.Impedances can be approximately 1.5-2.0× greater when the cryoballoon isin good contact. These measurements are reproducible across twodifferent pig measurements and across multiple trials runs in eachanimal.

The state of the contact sensors is assessed during cryoablation byfirst establishing adequate occlusion. Once occlusion is confirmed,cryoenergy is applied and changes in impedance are tracked over thecourse of 15-second intervals. The reaction of the conformal sensors isassessed since cooling happens gradually over 2-3 min time intervals.Impedance gradually rose by up to 25× across the active sensors. Thisresult highlights a second use-case scenario for impedance-based contactsensing whereby changes in impedance can track occlusion.

In the case where there may be a gap (poor occlusion), the sensorsaligned with regions of good occlusion freeze over (causing significantrise in impedance) while those near the gap experience heating effectsdue to flow of blood (causing an insignificant rise in impedance). Thisoutcome is tested in a few cases where a few of the sensors are occludedwhile others remained in poor contact. In this particularly case a fewof the sensor provided sensor results indicated that the sensors wereoccluded. This particular case shows how contact sensors on a ballooncan be used as a substitute for evaluating occlusion without use ofx-ray imaging.

Baseline impedance during contact can depend on salt concentration.Although impedance-based contact sensors are free from hysteresiseffects, they can cause variability based on the ionic concentration ofthe media. As a result, baseline impedance values could vary dependingon the salt concentration of blood relative to cardiac tissue or saline.The most significant challenges are in establishing the baseline levelsupon deployment of the catheter in heart. Once this baseline isestablished, occlusion is then quickly assessed upon balloonmaneuvering. Baseline automation strategies in software/DAQ dataacquisition system console can be implemented as a way to estimatebaseline levels across individual sensors once the cryoballoon inflatesin the atria.

FIG. 50 demonstrates an example user interface displaying binary readouts of sensors disposed on a balloon catheter. In the example of FIG.50, each circle corresponds to a sensing element, and provides arepresentation of a state of the sensing element. In this example, anopen circle on the display corresponds to no contact between a sensingelement and the tissue, and the shaded circle indicates an amount ofcontact between a sensing element and the tissue.

FIGS. 51A and 51B illustrate another example a visualization of contactsensing from measured data. Such visualization can help personnel inmaking assessments on occlusion. Specifically, FIG. 51A is a simplifiedrepresentation of the balloon cross section. Through color or texture ofthe small circles representing each sensor, the example user interfacecan be used to indicate whether a sufficient contact force isexperienced by a given sensing element. For example, a measured value ofthe sensing element above a threshold value can be decided as anindicator that the sensor has established contact with a portion oftissue, a measured value of the sensing element below the thresholdvalue can be decided as an indicator that the sensor has not establishedcontact with a portion of tissue. FIG. 51B is an example chartrepresentation of a measure of contact force experienced by each sensor.

While the user interface of FIGS. 50, 51A and 51B are described in termsof indication of contact force between the sensing elements and thetissue, the user interface and visualization technique can be applied todisplay the results of other measurements, including impedance,temperature, pressure, or any other type of measurement that sensingelements according to the principles herein can be used to measure.

FIG. 52 demonstrates another example user interface displaying binaryread outs of sensing elements disposed on an inflatable body (here aballoon catheter). In this example, an open circle on the displaycorresponds to no contact between a sensing element and the tissue, andthe shaded circle indicates an amount of contact between a sensingelement and the tissue

FIG. 53 demonstrates an example user interface displaying quantitativeread outs of sensing elements disposed on an inflatable body (here aballoon catheter In this example, a length of an arrow at each sensingelement representation serves as an indicator of the amount of ameasurement from the respective sensing element.

FIG. 54 demonstrates another example user interface displayingquantitative read outs of sensors disposed on a balloon catheter. Inthis example, the sensor representations are arranged in two differentdiameter circles, which can be used to indicate the spatial distributionof the sensing elements on the inflatable body. For example, the sensingelement representations in the smaller circle can be used to indicatemeasurements of sensing elements disposed closer to a top portion of theinflatable body; the sensing element representations in the largercircle can be used to indicate measurements of sensing elements disposedfarther from the top portion of the inflatable body. In this example, alength of an arrow at each sensing element representation serves as anindicator of the amount of a measurement from the respective sensingelement. A measurement below a threshold value can be classified as nocontact, while a measurement above the threshold value indicates anamount of contact.

FIGS. 55A-55B illustrate the principles of determining whether contactis made to blood or tissue based on changes in electrical conductivityor resistivity. FIG. 50 illustrates the principles of determiningwhether contact is made to blood or tissue based on changes inelectrical conductivity or resistivity. Specifically, because the bloodhas a higher resistivity than tissue (ρ_(blood)>ρ_(tissue)), using theconstant voltage sources illustrated in FIGS. 47 and 48, a greatervoltage across electrodes is measured when they are in contact withblood as compared with when they are in contact with tissue. As shownthe measured voltages result from AC current injection at apredetermined frequency.

FIG. 56 shows example PSR contact sensor in IVC/SVC data. The plot showsvalues of measurements that are determined to indicate no contact orcontact. In this example, a measurement above a threshold value ofaround 1.5 mV are taken to indicate contact between a sensing elementand an inflatable body. The example results show that PSR contactsensors tracked contact and non-contact settings but can be unstablecompared to in vitro recordings.

FIG. 57 illustrates example filtering of EIT data. FIG. 53 illustratesfiltered EIT data, where a low-pass Butterworth filter can be used toimprove signal quality without sacrificing contact information. Forexample, a filter can be applied to measurements to extract signal fromthe sensing elements from the noise in the measurements.

FIG. 58 illustrates example EIT contact sensors in IVC data. In thisexample, it is shown that measurements from sensing elements configuredas EIT sensors can be used to distinguish among sensing elements thatare in contact, no contact, or poor contact states in IVC. For example,a measurement below a first threshold value can be used to indicate astate of “no contact” for a sensing element. In this example, a valuebelow about 0.6 mV is determined as an indicator of “no contact.” Inanother example, a measurement above a second threshold value can beused to indicate a state of “contact” for a sensing element. In thisexample, a value above about 0.8 mV is determined as an indicator of“contact.” In another example, a measurement between the first thresholdvalue and the second threshold value can be used to indicate a state of“poor contact” for a sensing element. In this example, a value betweenabout 0.6 mV and about 0.8 mV is determined as an indicator of “poorcontact.”

FIGS. 59A-59C illustrates additional examples of sensing elementsconfigurations on the balloon surface, according to the principlesdescribed herein. Multiple independent flex boards can be used toincrease the total number of sensors. For example, FIGS. 59A-59Cillustrate that the flexible interconnects 5900 leading from the sensingelements 5901 can be routed down towards the base of the inflatablebody. FIG. 59A shows the sensing elements 5901 can be disposed along twodifferent latitudes of the inflatable body, and the coupling bus 5902can run sequentially from a sensing element at one latitude to a sensingelement in another latitude. FIG. 59B shows that the flexibleinterconnect 5900 can be routed down towards the base of the inflatablebody where a coupling bus 5920 may be located. FIG. 59C shows an examplethat includes more than one coupling bus. In this example, there arethree coupling buses 5952, 5954, 5956, each associated with a differentlatitude of the inflatable body. In this example, the sensing elements5901 are disposed along each of the three different latitudes of theinflatable body, and the sensing elements 5901 along each latitude areconnected with a respective coupling bus.

FIGS. 60A-60B illustrates further additional configurations of thesensing elements array, including “L” shaped arrays, according to theprinciples herein. For example, FIGS. 60A-60B illustrate that theflexible interconnects 6000 leading from the sensing elements 6001 canbe routed down towards the base of the inflatable body. FIG. 60A showsthat the sensing elements 6001 can be disposed along two differentlatitudes of the inflatable body, and the coupling bus 6002 can runbetween the two latitudes, with other flexible interconnects 6004. FIG.60B shows that the sensing elements 6001 can be disposed along twodifferent latitudes of the inflatable body, and each latitude can have arespective coupling bus 6010 and 6012, with a different flexibleinterconnect running to each respective coupling bus 6010 or 6012.

FIGS. 61A-61G illustrates examples of multi-sensing element (includingmultielectrode) devices and catheter devices. The devices in FIGS.61A-61D include passive wires with polyimide-based encapsulation. Thewires are exposed in select areas, thus forming electrode contacts. Theelectrode array can include, for example, 64 electrodes. FIGS. 61E-61Gshow the balloon-based ablation catheters that can be used to applycryo-, laser-, and high intensity ultrasound-forms of therapy whendeployed proximate to tissue. Any stretchable electronic systemaccording to the principles described herein can be disposed on any ofthe catheters shown in FIGS. 61A-61G.

A configuration of stretchable electronic system according to theprinciples herein can be disposed on the surface of any of these exampledevises according to the principles herein. The description hereinconcerning determining the areas of minimal curvature of the inflatablebody when in the deflated state can be applied to any of the exampledevices of FIGS. 61A-61G in going from a fully deployed state to acollapsed state (that has dimensions smaller than the fully deployedstate), including the netting shape surface.

Examples disclosed herein provide the benefits of the multi-electrodeconfiguration, and the advantages of balloon- and sheet-based platforms.High density mapping catheters are provided with deployable sheets. Thesheets can include high-density electronics (>64 sensory nodes) alongwith multiplexing and amplification circuitry, which are embedded on athin elastomeric or polymeric substrate. The substrate can havemicrofluidics channels 6100 (FIG. 60B) that are intricately patternedwith 10-100 μm channels used for delivering drugs, perfusates forcooling electronics or extremely cold or perfusates (alcohol, nitrousoxide (N₂O), etc.) for cryoablation.

FIG. 62 illustrates dense arrays of conformal electrodes with metalserpentine interconnects on thin polymeric sheets. The multi-electrodearray design (each electrode ˜100 μm² in surface area) allows forhigh-density spatial mapping of the interior surface of the heart.Electrodes are sub-micron (˜0.5-1 μm) in thickness and can includeonboard Si-based amplification circuits, row-select transistor-basedtransistor switches, along with other sensory structures, such astemperature and pressure sensors.

The example platform shown in FIG. 62 integrates a collection of sensorsand is deployable with a nitinol cage design. The underlying substratesare thin (<100 μm) and can be made of bioabsorbable material such assilk. Silk can serve as a temporary support for the various epicardialexamples disclosed herein.

FIGS. 63A-63C illustrate example endocardial applications of theapparatus and methods disclosed herein. FIG. 63A shows an image of arrayof electronics embedded on silk deployed on epicardial surface. FIG. 63Bshows conformal/stretchable electronics capture electrical signals withbroad areal coverage over 70-80% of the heart's anterior surface. FIG.63C show how the system contracts and expands with dynamic contractionsof the tissue (in this example, a live heart).

The EKG sensor array in FIGS. 63A-63C include 16 electrodes. Thisdensity can be increased to thousands, for example, using the samedemonstrated technology. The silk substrate dissolves within a fewminutes enabling intimate mechanical coupling between the beating heartand the backside surface of the array of conformal electronics. For EKGand other sensing types, this physical coupling of devices to thesurface of the heart can be beneficial. Another example that benefitsfrom intimate physical contact is an array of lateral strain sensorsthat record multidirectional movements of the heart.

FIGS. 64A-64C show examples of such a system including strainsensors/gauges. Specifically, FIG. 64A shows strain gauges thatimplement stretchable silicon in an interconnected array, FIG. 64B showsan image of eight (8) groups of sensors on an ECOFLEX®.(BASF, FlorhamPark, N.J.) substrate. FIG. 64C shows an image of an array on theepicardial beating heart.

One capability of the lateral strain gauges is in monitoring rhythmicmotions of the heart. The sensors can characterize multidirectionalmovements and sense heart rate increase, irregularities, or regions ofthe heart going through stress. Furthermore, the strain sensors candetect when the volume of the heart increases above its normal state,which can be an indication that the heart is suffering throughmyocardial infarct. This system can act as a ‘cardiac sleeve’ forimplantable devices or can be deployed in the endocardium to sense whenthe device contacts the walls of the heart.

FIGS. 65A-65C show other example sensing modalities includingtemperature sensors, and RF components for wireless communications. FIG.65A shows temperature sensor arrays co-located with sensing elements(including electrodes). The temperature sensors can be used to track lowtemperatures (to cryotemperatures) and high temperatures applied duringRF ablation. FIG. 65B shows temperature sensor and electrode arrays on asilk substrate for a low-temperature measurement. FIG. 65C showsexamples of applying the methods and apparatus with respect to cryolesion and RF lesion.

In various examples disclosed herein, therapeutic apparatus areconfigured in the ways described herein to provide ablative therapy,which may comprise an element capable of emitting various forms ofelectromagnetic radiation including microwave energy, thermal energy,laser, or radio frequency (RF) electromagnetic (EM) radiation.

In other examples, the element comprises an ultrasound emitter forultrasonic ablation. In such examples, the therapeutic facility (orelement thereof) comprises an array of ultrasound transducers (e.g.piezoelectric crystals). Each island comprises a receiver that sensesacoustic reflections generated by a source emitter that sends acousticwaves through the tissue at megahertz frequencies.

In still other examples, the device is configured to providecryo-ablation. Further, by coupling delivery channels and micro-valves6102 to the selectively operative circuitry in the manners describedherein, cryo-ablation may be delivered by the therapeutic facility orselected portions thereof.

In ablative examples, the substrate may be stretchable as disclosedabove and herein and provided with the stretchable circuitry describedherein. Also as described herein, the stretchable circuitry is able toremain functional upon conforming to the surface of the tissue, which inexamples for ablation, would comprise conformal contact with somesurface of the heart or cardiovascular system, including the ostium of apulmonary vein, any surface of a vein or artery, a septal wall of theheart, an atrial surface of a heart, or a ventricular surface of aheart.

All literature and similar material cited in this application,including, but not limited to, patents, patent applications, articles,books, treatises, and web pages, regardless of the format of suchliterature and similar materials, are expressly incorporated byreference in their entirety. In the event that one or more of theincorporated literature and similar materials differs from orcontradicts this application, including but not limited to definedterms, term usage, described techniques, or the like, this applicationcontrols.

While various inventive examples have been described and illustratedherein, those of ordinary skill in the art will readily envision avariety of other means and/or structures for performing the functionand/or obtaining the results and/or one or more of the advantagesdescribed herein, and each of such variations and/or modifications isdeemed to be within the scope of the inventive examples describedherein. More generally, those skilled in the art will readily appreciatethat all parameters, dimensions, materials, and configurations describedherein are meant to be exemplary and that the actual parameters,dimensions, materials, and/or configurations will depend upon thespecific application or applications for which the inventive teachingsis/are used. Those skilled in the art will recognize, or be able toascertain using no more than routine experimentation, many equivalentsto the specific inventive examples described herein. It is, therefore,to be understood that the foregoing examples are presented by way ofexample only and that, within the scope of the appended claims andequivalents thereto, inventive examples may be practiced otherwise thanas specifically described and claimed. Inventive examples of the presentdisclosure are directed to each individual feature, system, article,material, kit, and/or method described herein. In addition, anycombination of two or more such features, systems, articles, materials,kits, and/or methods, if such features, systems, articles, materials,kits, and/or methods are not mutually inconsistent, is included withinthe inventive scope of the present disclosure.

The above-described examples can be implemented in any of numerous ways.For example, some examples may be implemented using hardware, softwareor a combination thereof. When any aspect of an example is implementedat least in part in software, the software code can be executed on anysuitable processor or collection of processors, whether provided in asingle computer or distributed among multiple computers.

In this respect, various aspects may be embodied at least in part as acomputer readable storage medium (or multiple computer readable storagemedia) (e.g., a computer memory, one or more floppy discs, compactdiscs, optical discs, magnetic tapes, flash memories, circuitconfigurations in Field Programmable Gate Arrays or other semiconductordevices, or other tangible computer storage medium or non-transitorymedium) encoded with one or more programs that, when executed on one ormore computers or other processors, perform methods that implement thevarious examples of the technology described above. The computerreadable medium or media can be transportable, such that the program orprograms stored thereon can be loaded onto one or more differentcomputers or other processors to implement various aspects of thepresent technology as described above.

The terms “program” or “software” are used herein in a generic sense torefer to any type of computer code or set of computer-executableinstructions that can be employed to program a computer or otherprocessor to implement various aspects of the present technology asdescribed above. Additionally, it should be appreciated that accordingto one aspect of this example, one or more computer programs that whenexecuted perform methods of the present technology need not reside on asingle computer or processor, but may be distributed in a modularfashion amongst a number of different computers or processors toimplement various aspects of the present technology.

Computer-executable instructions may be in many forms, such as programmodules, executed by one or more computers or other devices. Generally,program modules include routines, programs, objects, components, datastructures, etc. that perform particular tasks or implement particularabstract data types. Typically the functionality of the program modulesmay be combined or distributed as desired in various examples.

Also, the technology described herein may be embodied as a method, ofwhich at least one example has been provided. The acts performed as partof the method may be ordered in any suitable way. Accordingly, examplesmay be constructed in which acts are performed in an order differentthan illustrated, which may include performing some acts simultaneously,even though shown as sequential acts in illustrative examples.

All definitions, as defined and used herein, should be understood tocontrol over dictionary definitions, definitions in documentsincorporated by reference, and/or ordinary meanings of the definedterms.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e., “one or more” ofthe elements so conjoined. Other elements may optionally be presentother than the elements specifically identified by the “and/or” clause,whether related or unrelated to those elements specifically identified.Thus, as a non-limiting example, a reference to “A and/or B”, when usedin conjunction with open-ended language such as “comprising” can refer,in one example, to A only (optionally including elements other than B);in another example, to B only (optionally including elements other thanA); in yet another example, to both A and B (optionally including otherelements); etc.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of” or “exactly one of,” or, when usedin the claims, “consisting of,” will refer to the inclusion of exactlyone element of a number or list of elements. In general, the term “or”as used herein shall only be interpreted as indicating exclusivealternatives (i.e. “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of,” “only one of,” or“exactly one of.” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one example, to at least one, optionally including more thanone, A, with no B present (and optionally including elements other thanB); in another example, to at least one, optionally including more thanone, B, with no A present (and optionally including elements other thanA); in yet another example, to at least one, optionally including morethan one, A, and at least one, optionally including more than one, B(and optionally including other elements); etc.

In the claims, as well as in the specification above, all transitionalphrases such as “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” “holding,” “composed of,” and the like are tobe understood to be open-ended, i.e., to mean including but not limitedto. Only the transitional phrases “consisting of” and “consistingessentially of” shall be closed or semi-closed transitional phrases,respectively, as set forth in the United States Patent Office Manual ofPatent Examining Procedures, Section 2111.03.

The claims should not be read as limited to the described order orelements unless stated to that effect. It should be understood thatvarious changes in form and detail may be made by one of ordinary skillin the art without departing from the spirit and scope of the appendedclaims. All examples that come within the spirit and scope of thefollowing claims and equivalents thereto are claimed.

The invention claimed is:
 1. A cryoablation apparatus comprising: aflexible substrate forming an inflatable cryoballoon; one or moredelivery channels coupled to the inflatable cryoballoon for delivering acryoablation fluid to the inflatable cryoballoon; a plurality of sensingelements disposed on the inflatable cryoballoon for sensing tissuetargeted for ablation, the plurality of sensing elements including aplurality of impedance sensing elements; a coupling bus disposed along alatitude of the inflatable cryoballoon and electrically coupled to theplurality of sensing elements; and an intermediate bus disposedlongitudinally along the inflatable cryoballoon and electricallycoupling the coupling bus to a measurement collection circuit forcollecting measurements from the plurality of sensing elements.
 2. Theapparatus of claim 1, wherein the plurality of sensing elements includesat least one pressure sensing element and at least one temperaturesensing element.
 3. The apparatus of claim 1, wherein the plurality ofsensing elements includes at least one pressure sensing element.
 4. Theapparatus of claim 1, wherein the plurality of sensing elements includesat least one temperature sensing element.
 5. The apparatus of claim 1,wherein the cryoablation fluid is alcohol or nitrous oxide.
 6. Theapparatus of claim 1, wherein the flexible substrate includes one ormore microchannels coupled to at least one delivery channel fordelivering the cryoablation fluid throughout the inflatable cryoballoon.7. The apparatus of claim 6, wherein at least one of the microchannelshas a diameter of 10 to 100 μm.
 8. The apparatus of claim 6, theapparatus further comprising: a shaft coupled to the inflatablecryoballoon including a first channel and a second channel, the firstchannel being in fluid communication with the inflatable cryoballoon toinflate the inflatable cryoballoon and the second channel being in fluidcommunication with the plurality of microchannels to deliver thecryoablation fluid to the plurality of microchannels.
 9. The apparatusof claim 1, wherein the plurality of impedance sensing elements includesa plurality of electrode pairs arranged in a circumferential orientationaround the inflatable cryoballoon, each electrode pair of the pluralityof electrode pairs being configured to measure an impedance between theelectrode pair.
 10. The apparatus of claim 9, wherein the impedanceindicates whether the inflatable cryoballoon is in conformal contactwith a surface of the tissue at the electrode pair on the inflatablecryoballoon.
 11. The apparatus of claim 9, wherein the circumferentialorientation of the plurality of sensing elements corresponds to acircumferential area of contact with a coronary vessel around theinflatable cryoballoon, with the inflatable cryoballoon in an inflatedstate.
 12. The apparatus of claim 1, wherein the plurality of sensingelements is disposed in a circumferential orientation along at least oneportion of the inflatable cryoballoon that experiences minimum strainwhen the inflatable cryoballoon is in a deflated state.
 13. Theapparatus of claim 1, wherein the plurality of sensing elements isconfigured to generate contact data representative of contact betweenthe plurality of sensing elements and the tissue.
 14. The apparatus ofclaim 6, further comprising: an electronic circuit embedded in oraffixed to the flexible substrate, the electronic circuit including theplurality of sensing elements.
 15. The apparatus of claim 14, furthercomprising: a plurality of micro-valves operatively connected to theelectronic circuit and fluidically connected to the one or moremicrochannels to selectively deliver the cryoablation fluid to selectedportions of the inflatable cryoballoon.
 16. The apparatus of claim 1,wherein the plurality of impedance sensing elements includes a pluralityof bipole electrodes configured to measure impedance differences. 17.The apparatus of claim 16, wherein each bipole electrode of theplurality of bipole electrodes is configured to inject current into asurface on which the bipole electrode is placed and measure a voltageacross the bipole electrode and another bipole electrode of theplurality of bipole electrodes.
 18. The apparatus of claim 1, whereinone or more sensing elements of the plurality of sensing elementsinclude one or more active components, one or more passive components,or a combination thereof.
 19. The apparatus of claim 18, wherein the oneor more active components include one or more amplifiers.
 20. Theapparatus of claim 1, wherein the plurality of sensing elements includeelectrical impedance tomography (EIT) contact sensors.
 21. The apparatusof claim 1, wherein the plurality of sensing elements includes one ormore lateral strain sensors, one or more temperature sensors, one ormore intracardiac electrogram (EGM) sensors, one or more light-emittingdiodes (LEDs), one or more multiplexors, one or more recordingelectrodes, one or more contact sensors, or a combination thereof.